c-Jun is a JNK-independent coactivator of the PU.1 transcription factor.
AuthorsBehre G; Whitmarsh A J; Coghlan M P; Hoang T; Carpenter C L; Zhang D E; Davis R J; Tenen D G;
JournalJ Biol Chem
PubMed ID9988737
The ETS domain transcription factor PU.1 is necessary for the development of monocytes and regulates, in particular, the expression of the monocyte-specific macrophage colony-stimulating factor (M-CSF) receptor, which is critical for monocytic cell survival, proliferation, and differentiation. The bZIP transcription factor c-Jun, which is part of the AP-1 transcription factor ... More
Receptor-selective effects of endogenous RGS3 and RGS5 to regulate mitogen-activated protein kinase activation in rat vascular smooth muscle cells.
AuthorsWang Qin; Liu Min; Mullah Bashar; Siderovski David P; Neubig Richard R;
JournalJ Biol Chem
PubMed ID12006602
Regulators of G protein signaling (RGS) proteins compose a highly diverse protein family best known for inhibition of G protein signaling by enhancing GTP hydrolysis by Galpha subunits. Little is known about the function of endogenous RGS proteins. In this study, we used synthetic ribozymes targeted to RGS2, RGS3, RGS5, ... More
The large size (six membrane-spanning repeats in each of four domains) and asymmetric architecture of the voltage-dependent Na+ channel has hindered determination of its structure. With the goal of determining the minimum structure of the Na+ channel permeation pathway, we created two stable cell lines expressing the voltage-dependent rat skeletal ... More
Vesicle-associated membrane protein-2/synaptobrevin binding to synaptotagmin I promotes O-glycosylation of synaptotagmin I.
AuthorsFukuda M.
JournalJ Biol Chem
PubMed ID12048209
Synaptotagmin I (Syt I), an evolutionarily conserved integral membrane protein of synaptic vesicles, is now known to regulate Ca2+-dependent neurotransmitter release. Syt I protein should undergo several post-translational modifications before maturation and subsequent functioning on synaptic vesicles (e.g. N-glycosylation and fatty acylation in vertebrate Syt I), because the apparent molecular ... More
Extracellular Export of Sphingosine Kinase-1 Enzyme. SPHINGOSINE 1-PHOSPHATE GENERATION AND THE INDUCTION OF ANGIOGENIC VASCULAR MATURATION.
AuthorsAncellin Nicolas; Colmont Chantal; Su Joseph; Li Qin; Mittereder Nanette; Chae Sung-Suk; Stefansson Steingrimur; Liau Gene; Hla Timothy;
JournalJ Biol Chem
PubMed ID11741921
The enzyme sphingosine kinase (SK) catalyzes the formation of sphingosine 1-phosphate (S1P), a bioactive lipid that acts extracellularly on G protein-coupled receptors of the S1P(1)/EDG-1 subfamily. Although S1P is formed in the cytosol of various cells, S1P release is not understood and is controversial because this lipid mediator is also ... More
Formation and removal of alpha-synuclein aggregates in cells exposed to mitochondrial inhibitors.
Authors Lee He-Jin; Shin Soon Young; Choi Chan; Lee Young Han; Lee Seung-Jae;
JournalJ Biol Chem
PubMed ID11724769
'Mitochondrial dysfunction has been associated with Parkinson''s disease. However, the role of mitochondrial defects in the formation of Lewy bodies, a pathological hallmark of Parkinson''s disease has not been addressed directly. In this report, we investigated the effects of inhibitors of the mitochondrial electron-transport chain on the aggregation of alpha-synuclein, ... More
Integrin-linked kinase regulates inducible nitric oxide synthase and cyclooxygenase-2 expression in an NF-kappa B-dependent manner.
Authors Tan Clara; Mui Alice; Dedhar Shoukat;
JournalJ Biol Chem
PubMed ID11724787
'Nitric oxide (NO) and prostaglandins are produced as a result of the stimulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2, respectively, in response to cytokines or lipopolysaccharide (LPS). We demonstrate that the activity of integrin-linked kinase (ILK) is stimulated by LPS activation in J774 macrophages. Inhibition of ILK activity ... More
A Novel Pathway for Nickel-induced Interleukin-8 Expression.
'Inhalation of particulate nickel subsulfide (Ni(3)S(2)) causes chronic active inflammation and fibrosis of the lungs. However, the mechanisms for these effects are not well understood. Therefore, cell culture experiments with BEAS-2B human airway epithelial cells were conducted to test the hypothesis that exposure to non-cytotoxic levels of Ni(3)S(2) induces expression ... More
Intracellular stability of anti-caspase-3 intrabodies determines efficacy in retargeting the antigen.
Authors Rajpal A; Turi T G;
JournalJ Biol Chem
PubMed ID11425853
'Although intracellular antibodies (intrabodies) are being explored as putative therapeutic and research reagents, little is known about the principles that dictate the efficacy of these molecules. In our efforts to address this issue, we generated a panel of five intrabodies, directed against catalytically inactive murine caspase-3, by screening single-chain antibody ... More
Synaptotagmin V is targeted to dense-core vesicles that undergo calcium-dependent exocytosis in PC12 cells.
'Synaptotagmins (Syts) III, V, VI, and X are classified as a subclass of Syt, based on their sequence similarities and biochemical properties (Ibata, K., Fukuda, M., and Mikoshiba, K. (1998) J. Biol. Chem. 273, 12267-12273; Fukuda, M., Kanno, E., and Mikoshiba, K. (1999) J. Biol. Chem. 274, 31421-31427). Although they ... More
Stimulation of p53-mediated transcriptional activation by the p53-binding proteins, 53BP1 and 53BP2.
Authors Iwabuchi K; Li B; Massa H F; Trask B J; Date T; Fields S;
JournalJ Biol Chem
PubMed ID9748285
'p53 is a tumor suppressor protein that controls cell proliferation by regulating the expression of growth control genes. In a previous study, we identified two proteins, 53BP1 and 53BP2, that are able to bind to wild type but not to mutant p53 via the DNA-binding domain of p53. We isolated ... More
Activation of retinoic acid receptor-dependent transcription by all-trans-retinoic acid metabolites and isomers.
Authors Idres Nadia; Marill Julie; Flexor Maria A; Chabot Guy G;
JournalJ Biol Chem
PubMed ID12070176
'We have shown that four metabolites of all-trans-retinoic acid (ATRA) (4-oxo-, 4-OH-, 18-OH-, and 5,6-epoxy-RA) can induce maturation of NB4 promyelocytic leukemia cells (Idres, N., Benoit, G., Flexor, M. A., Lanotte, M., and Chabot, G. G. (2001) Cancer Res. 61, 700-705). To better understand the mechanism of action of ATRA ... More
STAT3 down-regulates the expression of cyclin D during liver development.
'As the expression of cyclin D1 is induced during liver regeneration and also in hepatic tumor cells, cyclin D1 is likely to play an important role in the proliferation and transformation of hepatocytes. However, the role of cyclin D1 in liver development remains unknown. Here we show that the expression ... More
Fe65, a ligand of the Alzheimer's beta-amyloid precursor protein, blocks cell cycle progression by down-regulating thymidylate synthase expression.
'The functions of the Alzheimer''s beta-amyloid precursor protein (APP) and of its complex with the adaptor protein Fe65 are still unknown. We have demonstrated that Fe65 is also a nuclear protein and APP functions as an extranuclear anchor, thus preventing Fe65 nuclear translocation. According to this finding, it was also ... More
The transcription factors GATA4 and dHAND physically interact to synergistically activate cardiac gene expression through a p300-dependent mechanism.
Authors Dai Yan-Shan; Cserjesi Peter; Markham Bruce E; Molkentin Jeffery D;
JournalJ Biol Chem
PubMed ID11994297
'An intricate array of heterogeneous transcription factors participate in programming tissue-specific gene expression through combinatorial interactions that are unique to a given cell-type. The zinc finger-containing transcription factor GATA4, which is widely expressed in mesodermal and endodermal derived tissues, is thought to regulate cardiac myocyte-specific gene expression through combinatorial interactions ... More
Inhibition of phosphorylation of BAD and Raf-1 by Akt sensitizes human ovarian cancer cells to paclitaxel.
'We studied the roles of the phosphatidylinositol 3-kinase (PI-3K)-Akt-BAD cascade, ERK-BAD cascade, and Akt-Raf-1 cascade in the paclitaxel-resistant SW626 human ovarian cancer cell line, which lacks functional p53. Treatment of SW626 cells with paclitaxel activates Akt and ERK with different time frames. Interference with the Akt cascade either by treatment ... More
Interaction codes within the family of mammalian Phox and Bem1p domain-containing proteins.
AuthorsLamark T, Perander M, Outzen H, Kristiansen K, Øvervatn A, Michaelsen E, Bjørkøy G, Johansen T,
JournalJ Biol Chem
PubMed ID12813044
'The Phox and Bem1p (PB1) domain constitutes a recently recognized protein-protein interaction domain found in the atypical protein kinase C (aPKC) isoenzymes, lambda/iota- and zeta PKC; members of mitogen-activated protein kinase (MAPK) modules like MEK5, MEKK2, and MEKK3; and in several scaffold proteins involved in cellular signaling. Among the last ... More
Chromatin structural analyses of the mouse Igkappa gene locus reveal new hypersensitive sites specifying a transcriptional silencer and enhancer.
'To identify new regulatory elements within the mouse Igkappa locus, we have mapped DNase I hypersensitive sites (HSs) in the chromatin of B cell lines arrested at different stages of differentiation. We have focused on two regions encompassing 50 kilobases suspected to contain new regulatory elements based on our previous ... More
DNA sequence variation in the promoter region of the VEGF gene impacts VEGF gene expression and maximal oxygen consumption.
AuthorsPrior SJ, Hagberg JM, Paton CM, Douglass LW, Brown MD, McLenithan JC, Roth SM,
JournalAm J Physiol Heart Circ Physiol
PubMed ID16339827
'In its role as an endothelial cell proliferation and migration factor, vascular endothelial growth factor (VEGF) can affect peripheral circulation, and therefore impact maximal oxygen consumption (Vo2max). Because of the role of VEGF, and because variation in the VEGF gene has the ability to alter VEGF gene expression and VEGF ... More
Flavonoid inhibition of sodium-dependent vitamin C transporter 1 (SVCT1) and glucose transporter isoform 2 (GLUT2), intestinal transporters for vitamin C and Glucose.
Authors Song Jian; Kwon Oran; Chen Shenglin; Daruwala Rushad; Eck Peter; Park Jae B; Levine Mark;
JournalJ Biol Chem
PubMed ID11834736
'Vitamin C and flavonoids, polyphenols with uncertain function, are abundant in fruits and vegetables. We postulated that flavonoids have a novel regulatory action of delaying or inhibiting absorption of vitamin C and glucose, which are structurally similar. From six structural classes of flavonoids, at least 12 compounds were chosen for ... More
A novel tricomplex of BRCA1, Nmi, and c-Myc inhibits c-Myc-induced human telomerase reverse transcriptase gene (hTERT) promoter activity in breast cancer.
Authors Li Huchun; Lee Tae-Hee; Avraham Hava;
JournalJ Biol Chem
PubMed ID11916966
'Germ-line mutations in BRCA1 predispose individuals to breast and ovarian cancers. We observed a novel endogenous association of BRCA1 with Nmi (N-Myc-interacting protein) in breast cancer cells. Nmi was found to interact specifically with BRCA1, both in vitro and in vivo, by binding to two major domains in BRCA1, amino ... More
p38 kinase regulates nitric oxide-induced apoptosis of articular chondrocytes by accumulating p53 via NFkappa B-dependent transcription and stabilization by serine 15 phosphorylation.
Authors Kim Song-Ja; Hwang Sang-Gu; Shin Deug Y; Kang Shin-Sung; Chun Jang-Soo;
JournalJ Biol Chem
PubMed ID12091386
'Nitric oxide (NO) during primary culture of articular chondrocytes causes apoptosis via p38 mitogen-activated protein kinase in association with elevation of p53 protein level, caspase-3 activation, and differentiation status. In this study, we characterized the molecular mechanism by which p38 kinase induces apoptosis through activation of p53. We report here ... More
Localization of the secretory granule marker protein chromogranin B in the nucleus. Potential role in transcription control.
Authors Yoo Seung Hyun; You Soon Hee; Kang Moon Kyung; Huh Yang Hoon; Lee Choong Sik; Shim Chan Seob;
JournalJ Biol Chem
PubMed ID11854265
'Chromogranins A (CGA) and B (CGB) are two major Ca(2+) storage proteins of the secretory granules of neuroendocrine cells. Nevertheless, we found in the present study that CGB was also localized in the nucleus. In immunogold electron microscopy using bovine adrenal medullary chromaffin cells, it was found that the number ... More
The tumor suppressor protein TSLC1 is involved in cell-cell adhesion.
'TSLC1 is a tumor suppressor gene encoding a member of the immunoglobulin (Ig) superfamily. The significant homology of its extracellular domain with those of other Ig superfamily cell adhesion molecules (IgCAMs) has raised the possibility that TSLC1 participates in cell-cell interactions. In this study, the physiological properties of TSLC1 were ... More
Smad4/DPC4-dependent Regulation of Biglycan Gene Expression by Transforming Growth Factor-beta in Pancreatic Tumor Cells.
'Overexpression of the small leucine-rich proteoglycan biglycan (BGN) in fibrosis and desmoplasia results from enhanced activity of transforming growth factor-beta (TGF-beta). In pancreatic adenocarcinoma, the tumor cells themselves may contribute to BGN synthesis in vivo, since 8 of 18 different pancreatic carcinoma cell lines constitutively expressed BGN mRNA, as shown ... More
Loricrin expression in cultured human keratinocytes is controlled by a complex interplay between transcription factors of the Sp1, CREB, AP1, and AP2 families.
Authors Jang Shyh-Ing; Steinert Peter M;
JournalJ Biol Chem
PubMed ID12200429
'The major protein component of the cornified cell envelope barrier structure of the epidermis is loricrin, and it is expressed late during terminal differentiation in epidermal keratinocytes. We have previously shown that an AP1 site located in the proximal promoter region (position -55) is essential for human loricrin promoter activity ... More
The Binding Site for Channel Blockers That Rescue Misprocessed Human Long QT Syndrome Type 2 ether-a-gogo-related Gene (HERG) Mutations.
Authors Ficker Eckhard; Obejero-Paz Carlos A; Zhao Shuxia; Brown Arthur M;
JournalJ Biol Chem
PubMed ID11741928
'Mutations in the human ether-a-gogo-related gene (HERG) K(+) channel gene cause chromosome 7-linked long QT syndrome type 2 (LQT2), which is characterized by a prolonged QT interval in the electrocardiogram and an increased susceptibility to life-threatening cardiac arrhythmias. LQT2 mutations produce loss-of-function phenotypes and reduce I(Kr) currents either by the ... More
Role of loop structures of neuropsin in the activity of serine protease and regulated secretion.
'Neuropsin involved in neural plasticity in adult mouse brain is a member of the S1 (clan SA) family of serine proteases and forms characteristic surface loops surrounding the substrate-binding site (Kishi, T., Kato, M., Shimizu, T., Kato, K., Matsumoto, K., Yoshida, S., Shiosaka, S., and Hakoshima, T. (1999) J. Biol. ... More
Linking beta-catenin to androgen-signaling pathway.
Authors Yang Fajun; Li Xiaoyu; Sharma Manju; Sasaki Carl Y; Longo Dan L; Lim Bing; Sun Zijie;
JournalJ Biol Chem
PubMed ID11792709
'The androgen-signaling pathway is important for the growth and progression of prostate cancer cells. The growth-promoting effects of androgen on prostate cells are mediated mostly through the androgen receptor (AR). There is increasing evidence that transcription activation by AR is mediated through interaction with other cofactors. beta-Catenin plays a critical ... More
Caspase 3 activity is required for skeletal muscle differentiation.
Authors Fernando Pasan; Kelly John F; Balazsi Kim; Slack Ruth S; Megeney Lynn A;
JournalProc Natl Acad Sci U S A
PubMed ID12177420
'The cellular alterations associated with skeletal muscle differentiation share a high degree of similarity with key phenotypic changes usually ascribed to apoptosis. For example, actin fiber disassembly/reorganization is a conserved feature of both apoptosis and differentiating myoblasts and the conserved muscle contractile protein, myosin light chain kinase, is required for ... More
5'-,3'-inverted thymidine-modified antisense oligodeoxynucleotide targeting midkine. Its design and application for cancer therapy.
'Oligodeoxynucleotides modified at both 5''- and 3''-ends with inverted thymidine (5''-,3''-inverted T) were introduced as new reagents for antisense strategies. These modifications were performed to make the oligodeoxynucleotides resistant to nucleases. The effectiveness of these oligodeoxynucleotides was evaluated in terms of inhibition of synthesis of midkine (MK), a heparin-binding growth ... More
Palmitoylation of KChIP splicing variants is required for efficient cell surface expression of Kv4.3 channels.
Authors Takimoto Koichi; Yang Eun-Kyoung; Conforti Laura;
JournalJ Biol Chem
PubMed ID12006572
'The Ca(2+)-binding proteins KChIP1-4 (KChIP3 is also known as DREAM and calsenilin) act as auxiliary subunits for voltage-gated K(+) channels in the Kv4 family. Here we identify three splicing isoforms of rat KChIP2 with variable N-terminal peptides. The two longer isoforms, which contain the 32-amino acid peptide, produce larger increases ... More
Transcriptional Regulation of the Pituitary Vasopressin V1b Receptor Involves a GAGA-binding Protein.
'The role of CT repeats (inverted GAGA box) in the rat vasopressin V1b receptor (V1bR) promoter in the transcriptional regulation of this gene was studied in H32 hypothalamic cells, which express endogenous V1bR. Transfection of a 2.5-kb V1bR fragment (2161 bp upstream and 377 bp downstream of the proximal transcriptional ... More
Dexras1/AGS-1 inhibits signal transduction from the Gi-coupled formyl peptide receptor to Erk-1/2 MAP kinases.
Authors Graham Timothy E; Prossnitz Eric R; Dorin Richard I;
JournalJ Biol Chem
PubMed ID11751935
'Dexras1 is a novel GTP-binding protein (G protein) that was recently discovered on the basis of rapid mRNA up-regulation by glucocorticoids in murine AtT-20 corticotroph cells and in several primary tissues. The human homologue of Dexras1, termed activator of G protein signaling-1 (AGS-1), has been reported to stimulate signaling by ... More
Contribution of estrogen receptor alpha to oncogenic K-Ras-mediated NIH3T3 cell transformation and its implication for escape from senescence by modulating the p53 pathway.
'We previously reported that enhanced transcriptional activation of estrogen receptor alpha (ERalpha) contributed to [(12)Val]K-Ras-mediated NIH3T3 cell transformation. Functional inactivation of ERalpha by a dominant negative mutant of ERalpha (DNER) in the presence of activated K-Ras 4B mutant arrested the cell cycle at G(0)/G(1), subsequently provoking replicative cell senescence, finally ... More
Auto-ADP-ribosylation of Pseudomonas aeruginosa ExoS.
Authors Riese Matthew J; Goehring Udo-Michael; Ehrmantraut Mary E; Moss Joel; Barbieri Joseph T; Aktories Klaus; Schmidt Gudula;
JournalJ Biol Chem
PubMed ID11821389
'Pseudomonas aeruginosa Exoenzyme S (ExoS) is a bifunctional type-III cytotoxin. The N terminus possesses a Rho GTPase-activating protein (GAP) activity, whereas the C terminus comprises an ADP-ribosyltransferase domain. We investigated whether the ADP-ribosyltransferase activity of ExoS influences its GAP activity. Although the ADP-ribosyltransferase activity of ExoS is dependent upon FAS, ... More
The beta subunit determines the ion selectivity of the GABAA receptor.
Authors Jensen Marianne L; Timmermann Daniel B; Johansen Tina H; Schousboe Arne; Varming Thomas; Ahring Philip K;
JournalJ Biol Chem
PubMed ID12177063
'The gamma-aminobutyric acid, type A (GABA(A)) receptor is a chloride-conducting receptor composed of alpha, beta, and gamma subunits assembled in a pentameric structure forming a central pore. Each subunit has a large extracellular agonist binding domain and four transmembrane domains (M1-M4), with the second transmembrane (M2) domain lining the pore. ... More
Transforming Growth Factor-beta Stimulates Parathyroid Hormone-related Protein and Osteolytic Metastases via Smad and Mitogen-activated Protein Kinase Signaling Pathways.
Authors Kakonen Sanna-Maria; Selander Katri S; Chirgwin John M; Yin Juan Juan; Burns Suzanne; Rankin Wayne A; Grubbs Barry G; Dallas Mark; Cui Yong; Guise Theresa A;
JournalJ Biol Chem
PubMed ID11964407
'Transforming growth factor (TGF)-beta promotes breast cancer metastasis to bone. To determine whether the osteolytic factor parathyroid hormone-related protein (PTHrP) is the primary mediator of the tumor response to TGF-beta, mice were inoculated with MDA-MB-231 breast cancer cells expressing a constitutively active TGF-beta type I receptor. Treatment of the mice ... More
Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14.
AuthorsAmes RS, Sarau HM, Chambers JK, Willette RN, Aiyar NV, Romanic AM, Louden CS, Foley JJ, Sauermelch CF, Coatney RW, Ao Z, Disa J, Holmes SD, Stadel JM, Martin JD, Liu WS, Glover GI, Wilson S, McNulty DE, Ellis CE, Elshourbagy NA, Shabon U, Trill JJ, Hay DW, Douglas SA, et al
JournalNature
PubMed ID10499587
'Urotensin-II (U-II) is a vasoactive ''somatostatin-like'' cyclic peptide which was originally isolated from fish spinal cords, and which has recently been cloned from man. Here we describe the identification of an orphan human G-protein-coupled receptor homologous to rat GPR14 and expressed predominantly in cardiovascular tissue, which functions as a U-II ... More
Insulin Activates CCAAT/Enhancer Binding Proteins and Proinflammatory Gene Expression through the Phosphatidylinositol 3-Kinase Pathway in Vascular Smooth Muscle Cells.
'Phosphatidylinositol 3-kinase (PI3K) is a key molecule mediating signals of insulin in vascular smooth muscle cells (VSMCs). To examine the effect of chronic activation of PI3K on the gene expression of VSMCs, membrane-targeted p110CAAX, a catalytic subunit of PI3K, was overexpressed in rat VSMCs by adenovirus-mediated gene transfer. Similar to ... More
Use of a promoterless Renilla luciferase vector as an internal control plasmid for transient co-transfection assays of Ras-mediated transcription activation.
Authors Behre G; Smith L T; Tenen D G;
JournalBiotechniques
PubMed ID9894587
'not available'
An N-terminal arginine-rich cluster and a proline-alanine-threonine repeat region determine the cellular localization of the herpes simplex virus type 1 ICP34.5 protein and its ligand, protein phosphatase 1.
Authors Mao Hanwen; Rosenthal Kenneth S;
JournalJ Biol Chem
PubMed ID11788604
'The ICP34.5 protein facilitates herpes simplex virus replication by binding and activating protein phosphatase 1 (PP1) by means of a very conserved C-terminal GADD34-like region. Natural variants of the ICP34.5 differing in the number of arginines in an Arg-rich cluster at the N terminus and the number of Pro-Ala-Thr repeats ... More
p38 kinase-dependent and -independent Inhibition of protein kinase C zeta and -alpha regulates nitric oxide-induced apoptosis and dedifferentiation of articular chondrocytes.
AuthorsKim SJ, Kim HG, Oh CD, Hwang SG, Song WK, Yoo YJ, Kang SS, Chun JS.
JournalJ Biol Chem
PubMed ID12048219
'In articular chondrocytes, nitric oxide (NO) production triggers dedifferentiation and apoptotic cell death that is regulated by the converse functions of two mitogen-activated protein kinase subtypes, extracellular signal-regulated kinase (ERK) and p38 kinase. Since protein kinase C (PKC) transduces signals that influence differentiation, survival, and apoptosis of various cell types, ... More
PS1 N- and C-terminal fragments form a complex that functions in APP processing and Notch signaling.
Authors Levitan D; Lee J; Song L; Manning R; Wong G; Parker E; Zhang L;
JournalProc Natl Acad Sci U S A
PubMed ID11593035
'Presenilin proteins play critical roles in the proteolytic processing of both Notch and amyloid precursor protein (APP). Presenilin itself undergoes endoproteolytic processing to generate an N-terminal and C-terminal fragment. As demonstrated previously, overexpression of presenilin 1 (PS1) holoprotein does not change the levels of the N-terminal and C-terminal fragments (NTF ... More
A sensitive and quantitative assay for measuring cleavage of presenilin substrates.
'The presenilin (PS) proteins are components of the gamma-secretase activity, which is central in the pathogenesis of Alzheimer''s disease. Here we present a novel cell-based reporter gene assay for the quantification of PS-controlled gamma-secretase cleavage of the Alzheimer amyloid precursor protein (APP). We show that this assay offers several advantages, ... More
Ectopic expression of necdin induces differentiation of mouse neuroblastoma cells.
'Necdin is expressed predominantly in postmitotic neurons, and ectopic expression of this protein strongly suppresses cell growth. Necdin has been implicated in the pathogenesis of Prader-Willi syndrome, a human neurodevelopmental disorder associated with genomic imprinting. Here we demonstrate that ectopic expression of necdin induces a neuronal phenotype in neuroblastoma cells. ... More
The Ski protein family is required for MeCP2-mediated transcriptional repression.
Authors Kokura K; Kaul S C; Wadhwa R; Nomura T; Khan M M; Shinagawa T; Yasukawa T; Colmenares C; Ishii S;
JournalJ Biol Chem
PubMed ID11441023
'DNA methylation is essential for development in the mouse and plays an important role in inactivation of the X chromosome and genomic imprinting. MeCP2 is the founder member of a family of methyl-CpG-binding proteins. MeCP2 directly binds to the co-repressor mSin3, which interacts with class I histone deacetylase, recruiting them ... More
The organellular chloride channel protein CLIC4/mtCLIC translocates to the nucleus in response to cellular stress and accelerates apoptosis.
AuthorsSuh KS, Mutoh M, Nagashima K, Fernandez-Salas E, Edwards LE, Hayes DD, Crutchley JM, Marin KG, Dumont RA, Levy JM, Cheng C, Garfield S, Yuspa SH,
JournalJ Biol Chem
PubMed ID14610078
CLIC4/mtCLIC, a chloride intracellular channel protein, localizes to the mitochondria and cytoplasm of keratinocytes and participates in the apoptotic response to stress. We now show that multiple stress inducers cause the translocation of cytoplasmic CLIC4 to the nucleus. Immunogold electron microscopy and confocal analyses indicate that nuclear CLIC4 is detected ... More
Phosphorylation of critical serine residues in Gem separates cytoskeletal reorganization from down-regulation of calcium channel activity.
AuthorsWard Y, Spinelli B, Quon MJ, Chen H, Ikeda SR, Kelly K,
JournalMol Cell Biol
PubMed ID14701738
Gem is a small GTP-binding protein that has a ras-like core and extended chains at each terminus. The primary structure of Gem and other RGK family members (Rad, Rem, and Rem2) predicts a GTPase deficiency, leading to the question of how Gem functional activity is regulated. Two functions for Gem ... More
Efficient intracellular assembly of papillomaviral vectors.
Although the papillomavirus structural proteins, L1 and L2, can spontaneously coassemble to form virus-like particles, currently available methods for production of L1/L2 particles capable of transducing reporter plasmids into mammalian cells are technically demanding and relatively low-yield. In this report, we describe a simple 293 cell transfection method for efficient ... More
Growth inhibition by keratinocyte growth factor receptor of human salivary adenocarcinoma cells through induction of differentiation and apoptosis.
Authors Zhang Y; Wang H; Toratani S; Sato J D; Kan M; McKeehan W L; Okamoto T;
JournalProc Natl Acad Sci U S A
PubMed ID11562460
We have reported that normal human salivary gland-derived epithelial cells exclusively express keratinocyte growth factor receptor (KGFR). In the process of malignant transformation of human salivary gland tumors, KGFR gene expression disappeared concomitantly with the de novo expression of the fibroblast growth factor receptor 1 (FGFR1) and FGFR4 genes. In ... More
Specific inhibition of gene expression by small double-stranded RNAs in invertebrate and vertebrate systems.
Authors Caplen N J; Parrish S; Imani F; Fire A; Morgan R A;
JournalProc Natl Acad Sci U S A
PubMed ID11481446
Short interfering RNAs (siRNAs) are double-stranded RNAs of approximately 21-25 nucleotides that have been shown to function as key intermediaries in triggering sequence-specific RNA degradation during posttranscriptional gene silencing in plants and RNA interference in invertebrates. siRNAs have a characteristic structure, with 5'-phosphate/3'-hydroxyl ends and a 2-base 3' overhang on ... More
Mitochondrial Localization of Mutant Superoxide Dismutase 1 Triggers Caspase-dependent Cell Death in a Cellular Model of Familial Amyotrophic Lateral Sclerosis.
The mutations in superoxide dismutase 1 (SOD1) cause approximately 20% of familial amyotrophic lateral sclerosis cases. A toxic gain of function has been considered to be the cause of the disease, but its molecular mechanism remains uncertain. To determine whether the subcellular localization of mutant SOD1 is crucial to mutant ... More
Identification of a Neuronal Cdk5 Activator-binding Protein as Cdk5 Inhibitor.
Authors Ching Yick-Pang; Pang Andy S H; Lam Wing-Ho; Qi Robert Z; Wang Jerry H;
JournalJ Biol Chem
PubMed ID11882646
Neuronal Cdc2-like kinase (Nclk) plays an important role in a variety of cellular processes, including neuronal cell differentiation, apoptosis, neuron migration, and formation of neuromuscular junction. The active kinase consists of a catalytic subunit, Cdk5, and an essential regulatory subunit, neuronal Cdk5 activator (p35(nck5a) or p25(nck5a)), which is expressed primarily ... More
Tamapin, a venom peptide from the Indian red scorpion (Mesobuthus tamulus) that targets small conductance Ca2+-activated K+ channels and afterhyperpolarization currents in central neurons.
Authors Pedarzani Paola; D'hoedt Dieter; Doorty Kevina B; Wadsworth Jonathan D F; Joseph Jeremiah S; Jeyaseelan Kandiah; Kini R Manjunatha; Gadre S V; Sapatnekar S M; Stocker Martin; Strong Peter N;
JournalJ Biol Chem
PubMed ID12239213
The biophysical properties of small conductance Ca(2+)-activated K(+) (SK) channels are well suited to underlie afterhyperpolarizations (AHPs) shaping the firing patterns of a conspicuous number of central and peripheral neurons. We have identified a new scorpion toxin (tamapin) that binds to SK channels with high affinity and inhibits SK channel-mediated ... More
Apocytochrome c Blocks Caspase-9 Activation and Bax-induced Apoptosis.
Authors Martin Angel G; Fearnhead Howard O;
JournalJ Biol Chem
PubMed ID12393884
Complex networks of signaling pathways control the apoptotic response and, therefore, cell survival. However, these networks converge on a common machinery, of which the caspase cysteine proteases are key components. Diverse apoptotic stimuli release holocytochrome c from mitochondria, allowing holocytochrome c to bind apoptotic protease activating factor-1 (Apaf-1), which in ... More
Mediation of the DCC apoptotic signal by DIP13 alpha.
Authors Liu Jiayou; Yao Fayi; Wu Ruping; Morgan Michael; Thorburn Andrew; Finley Russell L Jr; Chen Yong Q;
JournalJ Biol Chem
PubMed ID12011067
DCC (deleted in colorectal cancer) is a candidate tumor suppressor gene. However the function of DCC remains elusive. Previously, we demonstrated that forced expression of DCC induces apoptosis or cell cycle arrest (Chen, Y. Q., Hsieh, J. T., Yao, F., Fang, B., Pong, R. C., Cipriano, S. C. & Krepulat, ... More
Identification and characterization of DEDD2, a death effector domain-containing protein.
A novel Death Effector Domain-containing protein was identified, DEDD2, which is closest in amino acid sequence homology to death effector domain-containing DNA-binding protein, DEDD. DEDD2 mRNA is expressed widely in adult human tissues with highest levels in liver, kidney, and peripheral blood leukocytes. DEDD2 interacts with FLIP, but not with ... More
Tumor-cell resistance to death receptor--induced apoptosis through mutational inactivation of the proapoptotic Bcl-2 homolog Bax.
The importance of Bax for induction of tumor apoptosis through death receptors remains unclear. Here we show that Bax can be essential for death receptor--mediated apoptosis in cancer cells. Bax-deficient human colon carcinoma cells were resistant to death-receptor ligands, whereas Bax-expressing sister clones were sensitive. Bax was dispensable for apical ... More
A novel phospholipase A1 with sequence homology to a mammalian Sec23p-interacting protein, p125.
p125, a mammalian Sec23p-interacting protein, exhibits sequence homology with bovine testis phosphatidic acid-preferring phospholipase A(1). In this study, we identified and characterized a new homologue of p125, KIAA0725p. KIAA0725p exhibited remarkable sequence similarity with p125 throughout the entire sequence determined but lacked an N-terminal proline-rich, Sec23p-interacting region. In vitro binding ... More
Analysis of a truncated form of cathepsin H in human prostate tumor cells.
Increased expression of proteases has been correlated with the malignant progression of a variety of tumors. We found a significant increase in cathepsin H expression in high-grade prostatic intraepithelial neoplasia and carcinoma of the prostate. Two forms of cathepsin H, the full-length form (CTSH) and a truncated form with a ... More
A novel human striated muscle RING zinc finger protein, SMRZ, interacts with SMT3b via its RING domain.
Authors Dai K S; Liew C C;
JournalJ Biol Chem
PubMed ID11283016
The RING domain is a conserved zinc finger motif, which serves as a protein-protein interaction interface. Searches of a human heart expressed sequence tag data base for genes encoding the RING domain identified a novel cDNA, named striated muscle RING zinc finger protein (SMRZ). The SMRZ cDNA is 1.9 kilobase ... More
Activation of BAD by therapeutic inhibition of epidermal growth factor receptor and transactivation by insulin-like growth factor receptor.
Authors Gilmore Andrew P; Valentijn Anthony J; Wang Pengbo; Ranger Ann M; Bundred Nigel; O'Hare Michael J; Wakeling Alan; Korsmeyer Stanley J; Streuli Charles H;
JournalJ Biol Chem
PubMed ID12011069
Novel cancer chemotherapeutics are required to induce apoptosis by activating pro-apoptotic proteins. Both epidermal growth factor (EGF) and insulin-like growth factor (IGF) provide potent survival stimuli in many epithelia, and activation of their receptors is commonly observed in solid human tumors. Here we demonstrate that blockade of the EGF receptor ... More
Galectin-12, an Adipose-expressed Galectin-like Molecule Possessing Apoptosis-inducing Activity.
Authors Hotta K; Funahashi T; Matsukawa Y; Takahashi M; Nishizawa H; Kishida K; Matsuda M; Kuriyama H; Kihara S; Nakamura T; Tochino Y; Bodkin N L; Hansen B C; Matsuzawa Y;
JournalJ Biol Chem
PubMed ID11435439
Galectins constitute a family of proteins that bind to beta-galactoside residues and have diverse physiological functions. Here we report on the identification of a galectin-like molecule, galectin-12, in a human adipose tissue cDNA library. The protein contained two potential carbohydrate-recognition domains with the second carbohydrate-recognition domain being less conserved compared ... More
A novel Dnmt3a isoform produced from an alternative promoter localizes to euchromatin and its expression correlates with active de novo methylation.
AuthorsChen T, Ueda Y, Xie S, Li E.
JournalJ Biol Chem
PubMed ID12138111
Previous studies have shown that the Dnmt3b gene encodes multiple variants via alternative splicing. However, only one form of Dnmt3a has been identified to date. We report here the discovery of a small form of Dnmt3a, denoted Dnmt3a2, from both human and mouse. The transcript encoding Dnmt3a2 is initiated from ... More
Calpain cleaves RhoA generating a dominant-negative form that inhibits integrin-induced actin filament assembly and cell spreading.
Authors Kulkarni Sucheta; Goll Darrel E; Fox Joan E B;
JournalJ Biol Chem
PubMed ID11964413
Integrin-induced cell adhesion results in transmission of signals that induce cytoskeletal reorganizations and resulting changes in cell behavior. The cytoskeletal reorganizations are regulated by transient activation and inactivation of Rho GTPases. Previously, we identified mu-calpain as an enzyme that is activated by signaling across beta1 and beta3 integrins. We showed ... More
Phosphotyrosine-specific phosphatase PTP-SL regulates the ERK5 signaling pathway.
AuthorsBuschbeck M, Eickhoff J, Sommer MN, Ullrich A.
JournalJ Biol Chem
PubMed ID12042304
The duration and the magnitude of mitogen-activated protein kinase (MAPK) activation specifies signal identity and thus allows the regulation of diverse cellular functions by the same kinase cascade. A tight and finely tuned regulation of MAPK activity is therefore critical for the definition of a specific cellular response. We investigated ... More
PATZ attenuates the RNF4-mediated enhancement of androgen receptor-dependent transcription.
PATZ is a transcriptional repressor affecting the basal activity of different promoters, whereas RNF4 is a transcriptional activator. The association of PATZ with RNF4 switches the activation to repression of selected basal promoters. Because RNF4 interacts also with the androgen receptor (AR) functioning as a coactivator and, in turn, RNF4 ... More
Differential signaling of cyclic AMP: opposing effects of exchange protein directly activated by cyclic AMP and cAMP-dependent protein kinase on protein kinase B activation.
Authors Mei Fang C; Qiao Jingbo; Tsygankova Oxana M; Meinkoth Judy L; Quilliam Lawrence A; Cheng Xiaodong;
JournalJ Biol Chem
PubMed ID11801596
The recent discovery of Epac, a novel cAMP receptor protein, opens up a new dimension in studying cAMP-mediated cell signaling. It is conceivable that many of the cAMP functions previously attributed to cAMP-dependent protein kinase (PKA) are in fact also Epac-dependent. The finding of an additional intracellular cAMP receptor provides ... More
Modulation of the Inward Rectifier Potassium Channel IRK1 by the Ras Signaling Pathway.
In this study, we investigated the role of Ras and the mitogen-activated protein kinase (MAPK) pathway in the modulation of the inward rectifier potassium channel IRK1. We show that although expression of IRK1 in HEK 293 cells leads to the appearance of a potassium current with strong inward rectifying properties, ... More
A Cyclic AMP-dependent Pathway Regulates the Expression of Acetylcholinesterase during Myogenic Differentiation of C2C12 Cells.
Authors Siow Nina L; Choi Roy C Y; Cheng Anthony W M; Jiang Joy X S; Wan David C C; Zhu Shang Q; Tsim Karl W K;
JournalJ Biol Chem
PubMed ID12140295
The expression of acetylcholinesterase (AChE) is markedly increased during myogenic differentiation of C2C12 myoblasts to myotubes; the expression is mediated by intrinsic factor(s) during muscle differentiation. In order to analyze the molecular mechanisms regulating AChE expression during myogenic differentiation, a approximately 2.2-kb human AChE promoter tagged with a luciferase reporter ... More
Sp1- and Sp3-mediated transcriptional regulation of the fibroblast growth factor receptor 1 gene in chicken skeletal muscle cells.
Authors Parakati Rajini; DiMario Joseph X;
JournalJ Biol Chem
PubMed ID11756440
Expression of the fibroblast growth factor receptor 1 (FGFR1) gene in skeletal muscle is positively regulated in proliferating myoblasts and declines during differentiation. We have characterized the cis-regulatory elements in the proximal region of the FGFR1 promoter which render positive transcriptional activity. Multiple elements between -69 and -14 activate the ... More
Accelerated phagocytosis of amyloid-beta by mouse and human microglia overexpressing the macrophage colony-stimulating factor receptor.
AuthorsMitrasinovic OM, Murphy GM Jr.
JournalJ Biol Chem
PubMed ID12032144
Microglia surrounding A beta plaques in Alzheimer's disease and in the APPV717F transgenic mouse model of Alzheimer's disease have enhanced immunoreactivity for the macrophage colony-stimulating factor receptor (M-CSFR), encoded by the proto-oncogene c-fms. Increased expression of M-CSFR on cultured microglia results in proliferation and release of pro-inflammatory cytokines and expression ... More
Cytoplasmic Prostaglandin E2 Synthase Is Dominantly Expressed in Cultured KAT-50 Thyrocytes, Cells That Express Constitutive Prostaglandin-endoperoxide H Synthase-2. BASIS FOR LOW PROSTAGLANDIN E2 PRODUCTION.
Authors Han Rui; Smith Terry J;
JournalJ Biol Chem
PubMed ID12145315
The recent identification and cloning of two glutathione-dependent prostaglandin E(2) synthase (PGES) genes has yielded important insights into the terminal step of PGE(2) synthesis. These enzymes form efficient functional pairs with specific members of the prostaglandin-endoperoxide H synthase (PGHS) family. Microsomal PGES (mPGES) is inducible and works more efficiently with ... More
Signaling molecules of the NF-kappa B pathway shuttle constitutively between cytoplasm and nucleus.
Authors Birbach Andreas; Gold Peter; Binder Bernd R; Hofer Erhard; de Martin Rainer; Schmid Johannes A;
JournalJ Biol Chem
PubMed ID11801607
We aimed to investigate the dynamics of the NF-kappaB signaling pathway in living cells using GFP variants of p65-NF-kappaB, IkappaBalpha, tumor necrosis factor-receptor associated factor 2 (TRAF2), the NF-kappaB inducing kinase (NIK) and IkappaB kinases (IKK1 and IKK2). Detailed kinetic analysis of constitutive nucleocytoplasmic shuttling processes revealed that IkappaBalpha enters ... More
ILPIP, a novel anti-apoptotic protein that enhances XIAP-mediated activation of JNK1 and protection against apoptosis.
AuthorsSanna MG, da Silva Correia J, Luo Y, Chuang B, Paulson LM, Nguyen B, Deveraux QL, Ulevitch RJ.
JournalJ Biol Chem
PubMed ID12048196
We have previously described a new aspect of the Inhibitor of Apoptosis (IAP) family of proteins anti-apoptotic activity that involves the TAK1/JNK1 signal transduction pathway (1,2). Our findings suggest the existence of a novel mechanism that regulates the anti-apoptotic activity of IAPs that is separate from caspase inhibition but instead ... More
Liganded androgen receptor interaction with beta-catenin: nuclear co-localization and modulation of transcriptional activity in neuronal cells.
Authors Pawlowski John E; Ertel Jessica R; Allen Melissa P; Xu Mei; Butler Cheryl; Wilson Elizabeth M; Wierman Margaret E;
JournalJ Biol Chem
PubMed ID11916967
A yeast two-hybrid assay was employed to identify androgen receptor (AR) protein partners in gonadotropin-releasing hormone neuronal cells. By using an AR deletion construct (AR-(Delta371-485)) as a bait, beta-catenin was identified as an AR-interacting protein from a gonadotropin-releasing hormone neuronal cell library. Immunolocalization of co-transfected AR and FLAG-beta-catenin demonstrated that ... More
Non-conventional trafficking of the cystic fibrosis transmembrane conductance regulator through the early secretory pathway.
Authors Yoo Jin-San; Moyer Bryan D; Bannykh Sergei; Yoo Hyeon-Mi; Riordan John R; Balch William E;
JournalJ Biol Chem
PubMed ID11799116
The mechanism(s) of cystic fibrosis transmembrane conductance regulator (CFTR) trafficking from the endoplasmic reticulum (ER) through the Golgi apparatus, the step impaired in individuals afflicted with the prevalent CFTR-DeltaF508 mutation leading to cystic fibrosis, is largely unknown. Recent morphological observations suggested that CFTR is largely absent from the Golgi in ... More
Fas ligand-independent, FADD-mediated activation of the Fas death pathway by anticancer drugs.
Authors Micheau O; Solary E; Hammann A; Dimanche-Boitrel M T;
JournalJ Biol Chem
PubMed ID10075697
Trimerization of the Fas receptor (CD95, APO-1), a membrane bound protein, triggers cell death by apoptosis. The main death pathway activated by Fas receptor involves the adaptor protein FADD (for Fas-associated death domain) that connects Fas receptor to the caspase cascade. Anticancer drugs have been shown to enhance both Fas ... More
Complex regulation of human neuronal nitric-oxide synthase exon 1c gene transcription. Essential role of Sp and ZNF family members of transcription factors.
Neuronal nitric-oxide synthase (nNOS) is expressed in a variety of human tissues and shows a complex transcriptional regulation with the presence of nine alternative first exons (1a-1i) resulting in nNOS transcripts with differing 5'-untranslated regions. We previously demonstrated that nNOS exon 1c, one of the predominant transcripts in the human ... More
CD40-mediated Activation of NF-kappa B in Airway Epithelial Cells.
Authors Propst Stacie M; Estell Kim; Schwiebert Lisa M;
JournalJ Biol Chem
PubMed ID12122011
We have reported previously that airway epithelial cells (AEC) express CD40 and that activation of this molecule stimulates the expression of inflammatory mediators, including the chemokine RANTES (regulated on activation normal T cell expressed and secreted). Because NF-kappaB regulates the expression of many inflammatory mediators, such as RANTES, we utilized ... More
Regulation of G Protein-linked Guanine Nucleotide Exchange Factors for Rho, PDZ-RhoGEF, and LARG by Tyrosine Phosphorylation. EVIDENCE OF A ROLE FOR FOCAL ADHESION KINASE.
A recently identified family of guanine nucleotide exchange factors for Rho that includes PDZ-RhoGEF, LARG, and p115RhoGEF exhibits a unique structural feature consisting in the presence of area of similarity to regulators of G protein signaling (RGS). This RGS-like (RGL) domain provides a structural motif by which heterotrimeric G protein ... More
Molecular cloning and functional characterization of murine sphingosine kinase.
Authors Kohama T; Olivera A; Edsall L; Nagiec M M; Dickson R; Spiegel S;
JournalJ Biol Chem
PubMed ID9726979
Sphingosine-1-phosphate (SPP) is a novel lipid messenger that has dual function. Intracellularly it regulates proliferation and survival, and extracellularly, it is a ligand for the G protein-coupled receptor Edg-1. Based on peptide sequences obtained from purified rat kidney sphingosine kinase, the enzyme that regulates SPP levels, we report here the ... More
Inhibition of neointimal formation after stent placement with adenovirus-mediated gene transfer of I kappa B alpha in the hypercholesterolemic rabbit model: initial results.
Authors Cejna Manfred; Breuss Johannes M; Bergmeister Helga; de Martin Rainer; Xu Zhongying; Grgurin Mario; Losert Udo; Plenk Hanns Jr; Binder Bernd R; Lammer Johannes;
JournalRadiology
PubMed ID12034938
PURPOSE: To evaluate the feasibility and efficacy of the local application of a replication-defective adenovirus construct for the expression of the antiinflammatory protein I kappa B alpha, inhibitor of nuclear factor kappa B (NF-kappa B), to reduce neointimal formation after stent placement. MATERIALS AND METHODS: Nitinol stents were implanted in ... More
Splitting the two pore domains from TOK1 results in two cationic channels with novel functional properties.
Potassium channels are membrane-spanning proteins with several transmembrane segments and a single pore region where ion conduction takes place (Biggin, P. C., Roosild, T., and Choe, S. (2000) Curr. Opin. Struct. Biol. 4, 456-461; Doyle, D. A., Morais Cabral, J., Pfuetzner, R. A., Kuo, A., Gulbis, J. M., Cohen, S. ... More
Glutathione levels and BAX activation during apoptosis due to oxidative stress in cells expressing wild-type and mutant cystic fibrosis transmembrane conductance regulator.
Cystic fibrosis is characterized by chronic inflammation and an imbalance in the concentrations of alveolar and lung oxidants and antioxidants, which result in cell damage. Modifications in lung glutathione concentrations are recognized as a salient feature of inflammatory lung diseases such as cystic fibrosis, and glutathione plays a major role ... More
Characterization of murine sphingosine-1-phosphate phosphohydrolase.
In the present study we have characterized mammalian sphingosine-1-phosphate phosphohydrolase (SPP1), an enzyme that specifically dephosphorylates sphingosine 1-phosphate (S1P) and which differs from previously described lipid phosphate phosphohydrolases. Based on sequence homology to murine SPP1, we cloned the human homolog. Transfection of human embryonic kidney 293 and Chinese hamster ovary ... More
Insulin-like growth factor-binding protein-5 (IGFBP-5) stimulates growth and IGF-I secretion in human intestinal smooth muscle by Ras-dependent activation of p38 MAP kinase and Erk1/2 pathways.
Authors Kuemmerle John F; Zhou Huiping;
JournalJ Biol Chem
PubMed ID11923300
Insulin-like growth factor-binding protein-5 (IGFBP-5) and insulin-like growth factor-I (IGF-I) are produced by human intestinal smooth muscle cells. Endogenous IGF-I stimulates growth and increases IGFBP-5 secretion. IGFBP-5 augments the effects of IGF-I by facilitating interaction of IGF-I with the IGF-I receptor tyrosine kinase. Andress (Andress, D. L. (1998) Am. J. ... More
Insulin-like Growth Factor (IGF)-binding Protein-3 Mutants That Do Not Bind IGF-I or IGF-II Stimulate Apoptosis in Human Prostate Cancer Cells.
Authors Hong Jiang; Zhang George; Dong Feng; Rechler Matthew M;
JournalJ Biol Chem
PubMed ID11784719
Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) can stimulate apoptosis and inhibit cell proliferation directly and independently of binding IGFs or indirectly by forming complexes with IGF-I and IGF-II that prevent them from activating the IGF-I receptor to stimulate cell survival and proliferation. To date, IGF-independent actions only have been demonstrated ... More
Mirk protein kinase is activated by MKK3 and functions as a transcriptional activator of HNF1alpha.
Authors Lim Seunghwan; Jin Kideok; Friedman Eileen;
JournalJ Biol Chem
PubMed ID11980910
Mirk/Dyrk1B is an arginine-directed serine/threonine protein kinase that is expressed at low levels in most normal tissues but at elevated levels in many tumor cell lines and in normal skeletal muscle. Colon carcinoma cell lines stably overexpressing Mirk proliferated in serum-free medium, but the mechanism of Mirk action is unknown. ... More