BACKGROUND: Reactive oxygen species, such as superoxide (O(2)(-)), are involved in the abnormal growth of various cell types. Angiotensin II (Ang II) is one of the most potent inducers of oxidative stress in the vasculature. The molecular events involved in Ang II-induced proliferation of vascular smooth muscle cells (VSMCs) are ... More
Functional interaction of caveolin-1 with Bruton's tyrosine kinase and Bmx.
Authors Vargas Leonardo; Nore Beston F; Berglof Anna; Heinonen Juhana E; Mattsson Pekka T; Smith C I Edvard; Mohamed Abdalla J;
JournalJ Biol Chem
PubMed ID11751885
'Bruton''s tyrosine kinase (Btk), a member of the Tec family of protein-tyrosine kinases, has been shown to be crucial for B cell development, differentiation, and signaling. Mutations in the Btk gene lead to X-linked agammaglobulinemia in humans and X-linked immunodeficiency in mice. Using a co-transfection approach, we present evidence here ... More
Repression of activator protein-1-mediated transcriptional activation by the Notch-1 intracellular domain.
Authors Chu Jianlin; Jeffries Shawn; Norton Jason E; Capobianco Anthony J; Bresnick Emery H;
JournalJ Biol Chem
PubMed ID11739397
'Developmental decisions that control cell fate are commonly regulated by the Notch signaling pathway. Activation of transmembrane Notch receptors results in proteolytic liberation of the intracellular domain of Notch, which translocates into the nucleus, binds a repressor (C promoter binding factor 1/RBP-Jkappa, Su(H), and Lag-1 (CSL)), and induces target genes. ... More
A differential role for the mitogen-activated protein kinases in lipopolysaccharide signaling: the MEK/ERK pathway is not essential for nitric oxide and interleukin 1beta production.
Authors Watters Jyoti J; Sommer Julie A; Pfeiffer Zachary A; Prabhu Usha; Guerra Alma N; Bertics Paul J;
JournalJ Biol Chem
PubMed ID11786532
'Endotoxin (lipopolysaccharide, LPS) is a component of the outer membrane of Gram-negative bacteria and promotes the activation of macrophages and microglia. Although these cells are highly LPS-responsive, they serve unique tissue-specific functions and exhibit different LPS sensitivities. Accordingly, it was of interest to evaluate whether these biological differences reside in ... More
Cholesteryl ester is transported from caveolae to internal membranes as part of a caveolin-annexin II lipid-protein complex.
Authors Uittenbogaard Annette; Everson William V; Matveev Sergey V; Smart Eric J;
JournalJ Biol Chem
PubMed ID11733519
'We previously demonstrated that in Chinese hamster ovary cells scavenger receptor, class B, type I-dependent selective cholesteryl ester uptake occurs in caveolae. In the present study we hypothesized that cholesteryl ester is transported from caveolae through the cytosol to an internal membrane by a caveolin chaperone complex similar to the ... More
Covalent attachment of the SUMO-1 protein to the negative regulatory domain of the c-Myb transcription factor modifies its stability and transactivation capacity.
Authors Bies Juraj; Markus Ján; Wolff Linda;
JournalJ Biol Chem
PubMed ID11779867
'The transcription factor c-Myb is subject to several types of post-translational modifications, including phosphorylation, acetylation, and ubiquitination. These modifications regulate the transcription and transforming activity as well as the proteolytic stability of c-Myb. Here we report the covalent modification of c-Myb with the small ubiquitin-related protein SUMO-1. Mutational analysis identified ... More
Inhibition of transforming growth factor beta signaling and Smad-dependent activation of transcription by the Latent Membrane Protein 1 of Epstein-Barr virus.
'Inhibition of transforming growth factor beta (TGFbeta) signaling by the Epstein-Barr virus Latent Membrane Protein 1 (LMP1) may account, at least in part, for the oncogenic activity of LMP1. We found that LMP1 is a potent inhibitor of TGFbeta signaling and Smad-dependent activation of transcription in 293 epithelial cells and ... 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
Cloning and characterization of freac-9 (FKHL17), a novel kidney-expressed human forkhead gene that maps to chromosome 1p32-p34.
'We describe the cloning of a near full-length cDNA of 4258 nucleotides encoding freac-9 (HGMW-approved symbol FKHL17), a novel human forkhead gene. The 5'' untranslated region is unusual since it is very long, 2127 nucleotides, and contains 15 upstream AUG codons. Hybridization to a panel consisting of RNA derived from ... More
Electrophoretic profiling of both RNA and protein from a single 250-pL sample.
Authors Zabzdyr Jennifer L; Lillard Sheri J;
JournalAnal Chem
PubMed ID11985318
'A novel approach is described that uses capillary electrophoresis (CE) to electrophoretically sample and separate both protein and RNA from a single injected plug of cell lysate. A 250-pL sample of lysate from Chinese hamster ovary cells (9.6 x 10(7) cells/mL) was hydrodynamically injected into a capillary containing a Tris-based ... More
Increases in free, unbound insulin-like growth factor I enhance insulin responsiveness in human hepatoma G2 cells in culture.
Authors Sakai Keiji; Lowman Henry B; Clemmons David R;
JournalJ Biol Chem
PubMed ID11834727
'Insulin-like growth factor-binding protein (IGFBP)-1 binds to insulin-like growth factor (IGF)-I and -II with high affinity and has been shown to modulate IGF-I actions in vivo and in vitro. The synthesis of IGFBP-1 is suppressed by insulin, and administration of IGFBP-1 to rats results in impaired glucose metabolism. A synthetic ... More
Characterization of the human cyclin-dependent kinase 2 gene. Promoter analysis and gene structure.
Authors Shiffman D; Brooks E E; Brooks A R; Chan C S; Milner P G;
JournalJ Biol Chem
PubMed ID8647814
'Cyclin-dependent kinase 2 is a serine/threonine protein kinase essential for progression of the mammalian cell cycle from G1 to S phase. CDK2 mRNA has been shown to be induced by serum in several cultured cell types. Therefore, we set out to identify elements that regulate the transcription of the human ... More
The cyclin-dependent kinase inhibitor p21WAF1/Cip1 is an antiestrogen-regulated inhibitor of Cdk4 in human breast cancer cells.
Authors Skildum Andrew J; Mukherjee Shibani; Conrad Susan E;
JournalJ Biol Chem
PubMed ID11741909
'The MCF-7 cell line is a model of estrogen-dependent, antiestrogen-sensitive human breast cancer. Antiestrogen treatment of MCF-7 cells causes dramatic decreases in both Cdk4 and Cdk2 activities, which leads to a G(1) phase cell cycle arrest. In this report, we investigate the mechanism(s) by which Cdk4 activity is regulated in ... More
Laminin alpha 3 LG4 module induces matrix metalloproteinase-1 through mitogen-activated protein kinase signaling.
AuthorsUtani A, Momota Y, Endo H, Kasuya Y, Beck K, Suzuki N, Nomizu M, Shinkai H,
JournalJ Biol Chem
PubMed ID12826666
'The LG4 module of the laminin alpha 3 chain (alpha 3 LG4), a component of epithelial-specific laminin-5, has cell attachment activity and binds syndecan (Utani, A., Nomizu, M., Matsuura, H., Kato, K., Kobayashi, T., Takeda, U., Aota, S., Nielsen, P. K., and Shinkai, H. (2001) J. Biol. Chem. 276, 28779-28788). ... More
Interleukin 24 (MDA-7/MOB-5) signals through two heterodimeric receptors, IL-22R1/IL-20R2 and IL-20R1/IL-20R2.
Authors Wang Mai; Tan Zhongjia; Zhang Rong; Kotenko Sergei V; Liang Peng;
JournalJ Biol Chem
PubMed ID11706020
'Interleukin 24 (IL-24) encodes a secreted protein that exhibits significant homology to the interleukin 10 (IL-10) family of cytokines. Here we show that the human IL-24 is secreted by activated peripheral blood mononuclear cells and is the ligand for two heterodimeric receptors, IL-22R1/IL-20R2 and IL-20R1/IL-20R2. The latter is also the ... More
Fibrin inhibits peripheral nerve remyelination by regulating schwann cell differentiation.
'Remyelination is a critical step for functional nerve regeneration. Here we show that fibrin deposition in the peripheral nervous system after injury is a key regulator of remyelination. After sciatic nerve crush, fibrin is deposited and its clearance correlates with remyelination. Fibrin induces phosphorylation of ERK1/2 and production of p75 ... More
A yersinia effector and a pseudomonas avirulence protein define a family of cysteine proteases functioning in bacterial pathogenesis.
Authors Shao Feng; Merritt Peter M; Bao Zhaoqin; Innes Roger W; Dixon Jack E;
JournalCell
PubMed ID12062101
'A Yersinia effector known as YopT and a Pseudomonas avirulence protein known as AvrPphB define a family of 19 proteins involved in bacterial pathogenesis. We show that both YopT and AvrPphB are cysteine proteases, and their proteolytic activities are dependent upon the invariant C/H/D residues conserved in the entire YopT ... More
Molecular rearrangements of the extracellular vestibule in NMDAR channels during gating.
Authors Sobolevsky Alexander I; Beck Christine; Wollmuth Lonnie P;
JournalNeuron
PubMed ID11779481
Many N-methyl-D-aspartate receptor (NMDAR) channel blockers that have therapeutic potential can be trapped in the closed state. Using a combination of the substituted cysteine accessibility method and open channel blockers, we found that the M3 segment forms the core of the extracellular vestibule, including a deep site for trapping blockers. ... More
Transcriptional induction of mitogen-activated protein kinase phosphatase 1 by retinoids. Selective roles of nuclear receptors and contribution to the antiapoptotic effect.
AuthorsXu Q, Konta T, Furusu A, Nakayama K, Lucio-Cazana J, Fine LG, Kitamura M,
JournalJ Biol Chem
PubMed ID12186877
All-trans-retinoic acid (t-RA) inhibits hydrogen peroxide (H(2)O(2))-induced apoptosis by inhibiting the c-Jun N-terminal kinase (JNK)-activator protein 1 (AP-1) pathway. In this report, we examined the involvement of mitogen-activated protein kinase phosphatase 1 (MKP-1) in suppression of JNK and the antiapoptotic effect of t-RA and the roles of nuclear receptors in ... More
Tissue-specific enhancer-promoter interactions regulate high level constitutive expression of matrix metalloproteinase 2 by glomerular mesangial cells.
Authors Harendza S; Pollock A S; Mertens P R; Lovett D H;
JournalJ Biol Chem
PubMed ID7642529
The 72-kDa gelatinase A (MMP-2) is a central mediator of the response of the intrinsic glomerular mesangial cell to inflammatory stimuli and is regulated in a unique, cell-specific manner. We isolated a 6-kilobase pair genomic fragment of the rat MMP-2 gene and sequenced and characterized 1686-base pair of the 5'-flanking ... More
Analysis of gene expression profile induced by hepatocyte nuclear factor 4alpha in hepatoma cells using an oligonucleotide microarray.
Hepatocyte nuclear factor 4alpha (HNF-4alpha), a liver-specific transcription factor, plays a significant role in many liver-specific functions, including lipid, glucose, drug, and ammonia metabolism, and also in embryonal liver development. However, its functions and regulation are not yet clearly understood. In this study, we constructed an adenovirus vector carrying rat ... More
Specific inhibition of ICAM-1 expression mediated by gene targeting with Triplex-forming oligonucleotides.
AuthorsBesch R, Giovannangeli C, Kammerbauer C, Degitz K
JournalJ Biol Chem
PubMed ID12080053
Selected sequences in the DNA double helix can be specifically recognized by oligonucleotides via hydrogen bonding interactions. The resulting triple helix can modulate DNA metabolism and especially interfere with transcription in a gene-specific manner. To explore the potential of triplex-forming oligonucleotides (TFOs) as gene repressors, a TFO was designed to ... More
Differential nucleocytoplasmic trafficking between the related endocytic proteins Eps15 and Eps15R.
Authors Poupon Viviane; Polo Simona; Vecchi Manuela; Martin Gwendal; Dautry-Varsat Alice; Cerf-Bensussan Nadine; Di Fiore Pier Paolo; Benmerah Alexandre;
JournalJ Biol Chem
PubMed ID11777906
Eps15 and Eps15R are constitutive components of clathrin-coated pits that are required for clathrin-dependent endocytosis. The most striking difference between these two related proteins is that Eps15R is also found in the nucleus, whereas Eps15 is excluded from this compartment at steady state. To better understand the individual functions of ... More
Fibroblast growth factor 1 regulates signaling via the glycogen synthase kinase-3beta pathway. Implications for neuroprotection.
We hypothesize that in neurodegenerative disorders such as Alzheimer's disease and human immunodeficiency virus encephalitis the neuroprotective activity of fibroblast growth factor 1 (FGF1) against several neurotoxic agents might involve regulation of glycogen synthase kinase-3beta (GSK3beta), a pathway important in determining cell fate. In primary rat neuronal and HT22 cells, ... More
Post-translational modifications of histones, in general, and acetylation/deacetylation, in particular, can dramatically alter gene expression in eukaryotic cells. In humans, four highly homologous class I HDAC enzymes (HDAC1, HDAC2, HDAC3, and HDAC8) have been identified to date. Although HDAC3 shares some structural and functional similarities with other class I HDACs, ... More
Cell docking and on-chip monitoring of cellular reactions with a controlled concentration gradient on a microfluidic device.
Authors Yang Mengsu; Li Cheuk-Wing; Yang Jun;
JournalAnal Chem
PubMed ID12199565
We have developed a microfluidic device for on-chip monitoring of cellular reactions. The device consists of two primary analytical functions: control of cell transport and immobilization, and dilution of an analyte solution to generate a concentration gradient. In this device, a dam structure in parallel to the fluid flow was ... More
Regulation of insulin-like growth factor I receptor dephosphorylation by SHPS-1 and the tyrosine phosphatase SHP-2.
Authors Maile Laura A; Clemmons David R;
JournalJ Biol Chem
PubMed ID11779860
Activation of insulin-like growth factor I receptor (IGF-IR) kinase is an important site of control of IGF-I-linked intracellular signaling pathways. One potentially important regulatory variable is IGF-IR dephosphorylation. It has been shown that SHP-2, a tyrosine phosphatase, can bind to the activated IGF-IR in vitro; however, its role in IGF-IR ... More
High density lipoprotein binding to scavenger receptor, Class B, type I activates endothelial nitric-oxide synthase in a ceramide-dependent manner.
Authors Li Xiang-An; Titlow William B; Jackson Brian A; Giltiay Nathalia; Nikolova-Karakashian Mariana; Uittenbogaard Annette; Smart Eric J;
JournalJ Biol Chem
PubMed ID11792700
Recently it has been demonstrated that high density lipoprotein (HDL) binding to scavenger receptors, class B, type I (SR-BI) stimulates endothelial nitric-oxide synthase (eNOS) activity. In the present studies we used a Chinese hamster ovary cell system and a human microvascular endothelial cell line to confirm that HDL stimulates eNOS ... More
A transmembrane tight junction protein selectively expressed on endothelial cells and platelets.
Searching for cell surface proteins expressed at interendothelial cell contacts, we have raised monoclonal antibodies against intact mouse endothelial cells. We obtained two monoclonal antibodies, 1G8 and 4C10, that stain endothelial cell contacts and recognize a protein of 55 kDa. Purification and identification by mass spectrometry of this protein revealed ... More
Endogenous G Protein-coupled Receptor Kinase 6 Regulates M3 Muscarinic Acetylcholine Receptor Phosphorylation and Desensitization in Human SH-SY5Y Neuroblastoma Cells.
Authors Willets Jonathon M; Challiss R A John; Nahorski Stefan R;
JournalJ Biol Chem
PubMed ID11856737
We have previously shown that overexpression of G protein-coupled receptor kinase 6 (GRK6) enhanced the phosphorylation and desensitization of the endogenously expressed M(3) muscarinic acetylcholine (mACh) receptor in human SH-SY5Y neuroblastoma cells. In this study we have examined the potential role of endogenous GRK6 in the regulation of M(3) mACh ... More
Influence of second and third cytoplasmic loops on binding, internalization, and coupling of chimeric bombesin/m3 muscarinic receptors.
Authors Tseng M J; Coon S; Stuenkel E; Struk V; Logsdon C D;
JournalJ Biol Chem
PubMed ID7629092
In order to investigate the molecular basis for differences in the characteristics of bombesin (Bn) and m3 muscarinic cholinergic (m3 ACh) receptors, chimeric Bn receptors possessing cytoplasmic domains from the m3 ACh receptor were produced. The receptors were expressed in CHO-K1 cells and binding, structural, and signal transduction characteristics were ... More
Cysteine string protein interacts with and modulates the maturation of the cystic fibrosis transmembrane conductance regulator.
Authors Zhang Hui; Peters Kathryn W; Sun Fei; Marino Christopher R; Lang Jochen; Burgoyne Robert D; Frizzell Raymond A;
JournalJ Biol Chem
PubMed ID12039948
The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated chloride channel whose phosphorylation regulates both channel gating and its trafficking at the plasma membrane. Cysteine string proteins (Csps) are J-domain-containing, membrane-associated proteins that have been functionally implicated in regulated exocytosis. Therefore, we evaluated the possibility that Csp is involved ... More
Malignant effusions and immunogenic tumour-derived exosomes.
BACKGROUND: Exosomes derived from tumours are small vesicles released in vitro by tumour cell lines in culture supernatants. To assess the role of these exosomes in vivo, we examined malignant effusions for their presence. We also investigated whether these exosomes could induce production of tumour-specific T cells when pulsed with ... More
Reduced interleukin-18 levels in BAL specimens from patients with asthma compared to patients with sarcoidosis and healthy control subjects.
Authors Ho Ling-Pei; Davis Margaret; Denison Alan; Wood Fraser T; Greening Andrew P;
JournalChest
PubMed ID12006423
STUDY OBJECTIVES: To investigate whether differing airway interleukin (IL)-18 levels may be implicated in the pathogenesis of asthma and sarcoidosis. SETTING: University teaching hospital. Patients and methods: IL-18 levels were measured in BAL fluid and in the supernatant of lipopolysaccharide (LPS)-stimulated alveolar macrophages obtained by BAL from 15 patients with ... More
Mechanisms of regulation of phospholipase d1 and d2 by the heterotrimeric g proteins g13 and gq.
Authors Xie Zhi; Ho Wan-Ting; Spellman Rachel; Cai Songmin; Exton John H;
JournalJ Biol Chem
PubMed ID11812783
Our earlier studies of rat brain phospholipase D1 (rPLD1) showed that the enzyme could be activated in cells by alpha subunits of the heterotrimeric G proteins G(13) and G(q). Recently, we showed that rPLD1 is modified by Ser/Thr phosphorylation and palmitoylation. In this study, we first investigated the roles of ... More
Brief exposure to high-dose transforming growth factor-beta1 enhances periosteal chondrogenesis in vitro: a preliminary report.
BACKGROUND: Articular cartilage has limited potential for repair. There have been various attempts aimed at improving the repair process in articular cartilage. Transforming growth factor-beta1 (TGF-beta1) has a stimulatory effect on chondrogenesis in periosteal explants. The purpose of the present study was to determine the effect of brief exposures (i.e., ... More
The minor subunit splice variants, H2b and H2c, of the human asialoglycoprotein receptor are present with the major subunit H1 in different hetero-oligomeric receptor complexes.
Authors Yik Jasper H N; Saxena Amit; Weigel Paul H;
JournalJ Biol Chem
PubMed ID11943787
The hepatic asialoglycoprotein receptor (ASGP-R) is an endocytic receptor that mediates the internalization of desialylated glycoproteins and their delivery to lysosomes. The human ASGP-R is a hetero-oligomeric complex composed of H1 and H2 subunits. There are three naturally occurring H2 splice variants, designated H2a, H2b, and H2c, although the expression ... More
A 2-D liquid separations/mass mapping method for interlysate comparison of ovarian cancers.
Authors Kachman Maureen T; Wang Haixing; Schwartz Donald R; Cho Kathleen R; Lubman David M;
JournalAnal Chem
PubMed ID11985308
A two-dimensional liquid phase separation of proteins from whole cell lysates coupled on-line to an electrospray-ionization time-of-flight (ESI-TOF) mass spectrometer (MS) is used to map the protein content of ovarian surface epithelial cells (OSE) and an ovarian carcinoma-derived cell line (ES2). The two dimensions involve the use of liquid isoelectric ... More
BCG-induced increase in interferon-gamma response to mycobacterial antigens and efficacy of BCG vaccination in Malawi and the UK: two randomised controlled studies.
Authors Black Gillian F; Weir Rosemary E; Floyd Sian; Bliss Lyn; Warndorff David K; Crampin Amelia C; Ngwira Bagrey; Sichali Lifted; Nazareth Bernadette; Blackwell Jenefer M; Branson Keith; Chaguluka Steven D; Donovan Linda; Jarman Elizabeth; King Elizabeth; Fine Paul E M; Dockrell Hazel M;
JournalLancet
PubMed ID11978337
BACKGROUND: The efficacy of BCG vaccines against pulmonary tuberculosis varies between populations, showing no protection in Malawi but 50-80% protection in the UK. To investigate the mechanism underlying these differences, randomised controlled studies were set up to measure vaccine-induced immune responsiveness to mycobacterial antigens in both populations. METHODS: 483 adolescents ... More
HIF-1<alpha> Repression of PTEN Transcription Mediates Protective Effects of BMSCs on Neurons During Hypoxia.
AuthorsYang X, Zhong M, Chen J, Li T, Cheng Q, Dai Y
JournalNeuroscience
PubMed ID30267829
Neonatal hypoxic-ischemic brain damage (HIBD) is a cerebral hypoxic-ischemic disease caused by a variety of insults during the perinatal period, leading to varying degrees of cognitive dysfunction. Mesenchymal stem cells play an important role in functional recovery, but the mechanism is not yet clear. It has been reported that HIF-1<alpha> ... More
JAK3 and PI3K mediate bovine Interferon-tau stimulated gene expression in the blood neutrophils.
AuthorsSheikh AA, Hooda OK, Dang AK
JournalJ Cell Physiol
PubMed ID29194593
Interferon tau, a 23?kDa trophoblast derived protein diffuses out from the uterus into the circulation and leads to the expression of IFNt stimulated genes viz. ISG15 and OAS1 in blood neutrophils. The IFNt pathway is species as well as tissue specific. To unsnarl the IFNt downstream signaling pathway, the blood ... More
Propagation of Brazilian Zika virus strains in static and suspension cultures using Vero and BHK cells.
AuthorsNikolay A, Castilho LR, Reichl U, Genzel Y
JournalVaccine
PubMed ID28343780
The recent spread of Zika virus (ZIKV) in the Americas and the Pacific has reached alarming levels in more than 60 countries. However, relatively little is known about the disease on a virological and epidemiological level and its consequences for humans. Accordingly, a large demand for in vitro derived Brazilian ... More
Human Synovial MSC Good Manufacturing Practices for Articular Cartilage Regeneration.
AuthorsFernandes TL, Kimura HA, Pinheiro CCG, Shimomura K, Nakamura N, Ferreira JRM, Gomoll AH, Hernandez AJ, Bueno DF,
JournalTissue Eng Part C Methods
PubMed ID30412046
cartilage restoration is a desperately needed bridge for patients with symptomatic cartilage lesions. Chondral lesion is a pathology with high prevalence, reaching as much as 63% of general population and 36% among athletes. Despite Autologous Chondrocyte Implantation (ACI) versatility, it still fails to fully reproduce hyaline articular cartilage characteristics. Mesenchymal ... More