An SH2 domain-containing 5' inositolphosphatase inhibits insulin-induced GLUT4 translocation and growth factor-induced actin filament rearrangement.
AuthorsVollenweider P, Clodi M, Martin SS, Imamura T, Kavanaugh WM, Olefsky JM
JournalMol Cell Biol
PubMed ID9891043
'Tyrosine kinase receptors lead to rapid activation of phosphatidylinositol 3-kinase (PI3 kinase) and the subsequent formation of phosphatidylinositides (PtdIns) 3,4-P2 and PtdIns 3,4, 5-P3, which are thought to be involved in signaling for glucose transporter GLUT4 translocation, cytoskeletal rearrangement, and DNA synthesis. However, the specific role of each of these ... More
Targeting of EBNA1 for rapid intracellular degradation overrides the inhibitory effects of the Gly-Ala repeat domain and restores CD8+ T cell recognition.
Authors Tellam J; Sherritt M; Thomson S; Tellam R; Moss D J; Burrows S R; Wiertz E; Khanna R;
JournalJ Biol Chem
PubMed ID11435434
'Epstein-Barr virus (EBV)-encoded nuclear antigen 1 (EBNA1) includes a unique glycine-alanine repeat domain that inhibits the endogenous presentation of cytotoxic T lymphocyte (CTL) epitopes through the class I pathway by blocking proteasome-dependent degradation of this antigen. This immune evasion mechanism has been implicated in the pathogenesis of EBV-associated diseases. Here, ... More
The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory.
'Many central neurons possess large acid-activated currents, yet their molecular identity is unknown. We found that eliminating the acid sensing ion channel (ASIC) abolished H(+)-gated currents in hippocampal neurons. Neuronal H(+)-gated currents and transient acidification are proposed to play a role in synaptic transmission. Investigating this possibility, we found ASIC ... More
Changes in glucose transport and water permeability resulting from the T310I pathogenic mutation in Glut1 are consistent with two transport channels per monomer.
AuthorsPavel Iserovich, Dong Wang, Li Ma, Hong Yang, Felipe A. Zuniga, Juan M. Pascual, Kunyan Kuang, Darryl C. De Vivo, Jorge Fischbarg
JournalJ Biol Chem
PubMed ID12032147
'We studied glucose and water passage across wild type (WT) glucose transporter Glut1 and its T310I pathogenic mutant, expressing them in Xenopus laevis oocytes. We found that the T310I mutation produced a 8-fold decrease in glucose transport (zero-trans influx, 13 +/- 2% compared with WT), accompanied by a 2.8-fold increase ... More
Translocation-arrested apolipoprotein B evades proteasome degradation via a sterol-sensitive block in ubiquitin conjugation.
AuthorsDu EZ, Fleming JF, Wang SL, Spitsen GM, Davis RA
JournalJ Biol Chem
PubMed ID9880570
'In this study, we explored how sterol metabolism altered by the expression of cholesterol-7alpha-hydroxylase NADPH:oxygen oxidoreductase (7alpha-hydroxylase) affects the ubiquitin-dependent proteasome degradation of translocation-arrested apoB53 in Chinese hamster ovary cells. Stable expression of two different plasmids that encode either rat or human 7alpha-hydroxylase inhibited the ubiquitin conjugation of apoB and ... More
Autoinhibition and isoform-specific dominant negative inhibition of the type II cGMP-dependent protein kinase.
AuthorsTaylor MK, Ahmed R, Begley M, Uhler MD,
JournalJ Biol Chem
PubMed ID12093798
'In the absence of cyclic nucleotides, the cAMP-dependent protein kinase and cGMP-dependent protein kinases (cGKs) suppress phosphotransfer activity at the catalytic cleft by competitive inhibition of substrate binding with a pseudosubstrate sequence within the holoenzyme. The magnitude of inhibition can be diminished by autophosphorylation near this pseudosubstrate sequence. Activation of ... More
Ca2+-dependent synaptotagmin binding to SNAP-25 is essential for Ca2+-triggered exocytosis.
AuthorsZhang X, Kim-Miller MJ, Fukuda M, Kowalchyk JA, Martin TF,
JournalNeuron
PubMed ID12062043
'Synaptotagmin is a proposed Ca2+ sensor on the vesicle for regulated exocytosis and exhibits Ca2+-dependent binding to phospholipids, syntaxin, and SNAP-25 in vitro, but the mechanism by which Ca2+ triggers membrane fusion is uncertain. Previous studies suggested that SNAP-25 plays a role in the Ca2+ regulation of secretion. We found ... More
Distinct dynamin-dependent and -independent mechanisms target structurally homologous dopamine receptors to different endocytic membranes.
AuthorsVickery RG, von Zastrow M
JournalJ Cell Biol
PubMed ID9885242
'D1 and D2 dopamine receptors are structurally homologous G protein- coupled receptors that serve distinct physiological functions both in neurons and nonneural cell types. We have observed that these receptors are selectively endocytosed in HEK293 cells by distinct dynamin- dependent and -independent mechanisms. Although these endocytic mechanisms operate with similarly ... More
Heterogeneous ribonucleoprotein A1 is part of an exon-specific splice-silencing complex controlled by oncogenic signaling pathways.
AuthorsMatter N, Marx M, Weg-Remers S, Ponta H, Herrlich P, König H,
JournalJ Biol Chem
PubMed ID10958793
Regulation of alternative pre-mRNA splicing, recognized as increasingly important in causing human disease, was studied using the CD44 gene, whose splice variants have been implicated in tumor progression. We identified heterogeneous ribonucleoprotein (hnRNP) A1 as a protein interacting in vitro and in vivo with regulatory splice elements in CD44 variant ... More
Parallel single-cell monitoring of receptor-triggered membrane translocation of a calcium-sensing protein module.
Authors Teruel Mary N; Meyer Tobias;
JournalScience
PubMed ID11884760
Time courses of translocation of fluorescently conjugated proteins to the plasma membrane were simultaneously measured in thousands of individual rat basophilic leukemia cells. We found that the C2 domain---a calcium-sensing, lipid-binding protein module that is an essential regulator of protein kinase C and numerous other proteins---targeted proteins to the plasma ... More
Conversion of proepithelin to epithelins: roles of SLPI and elastase in host defense and wound repair.
Increased leukocyte elastase activity in mice lacking secretory leukocyte protease inhibitor (SLPI) leads to impaired wound healing due to enhanced activity of TGFbeta and perhaps additional mechanisms. Proepithelin (PEPI), an epithelial growth factor, can be converted to epithelins (EPIs) in vivo by unknown mechanisms with unknown consequences. We found that ... More
Somatostatin receptor subtype 2 sensitizes human pancreatic cancer cells to death ligand-induced apoptosis.
AuthorsGuillermet J, Saint-Laurent N, Rochaix P, Cuvillier O, Levade T, Schally AV, Pradayrol L, Buscail L, Susini C, Bousquet C,
JournalProc Natl Acad Sci U S A
PubMed ID12490654
Somatostatin receptor subtype 2 (sst2) gene expression is lost in 90% of human pancreatic adenocarcinomas. We previously demonstrated that stable sst2 transfection of human pancreatic BxPC-3 cells, which do not endogenously express sst2, inhibits cell proliferation, tumorigenicity, and metastasis. These sst2 effects occur as a consequence of an autocrine sst2-dependent ... More
The prolyl isomerase Pin1 is a regulator of p53 in genotoxic response.
AuthorsZheng H, You H, Zhou XZ, Murray SA, Uchida T, Wulf G, Gu L, Tang X, Lu KP, Xiao ZX,
JournalNature
PubMed ID12397361
p53 is activated in response to various genotoxic stresses resulting in cell cycle arrest or apoptosis. It is well documented that DNA damage leads to phosphorylation and activation of p53 (refs 1-3), yet how p53 is activated is still not fully understood. Here we report that DNA damage specifically induces ... More
Dec1 and Dec2 are regulators of the mammalian molecular clock.
AuthorsHonma S, Kawamoto T, Takagi Y, Fujimoto K, Sato F, Noshiro M, Kato Y, Honma K,
JournalNature
PubMed ID12397359
The circadian rhythms in mammals are regulated by a pacemaker located in the suprachiasmatic nucleus of the hypothalamus. Four clock-gene families have been found to be involved in a transcription-translation feedback loop that generates the circadian rhythm at the intracellular level. The proteins Clock and Bmal1 form a heterodimer which ... More
Chimeras were previously generated between the ecotropic (Moloney-MuLV) and amphotropic (4070A) SU and TM proteins of murine leukemia virus (MuLV). After passage in D17 cells, three chimeras with junctions in the C terminus of SU (AE5, AE6, and AE7), showed improved kinetics of viral spreading, suggesting that they had adapted. ... More
Human lysophosphatidic acid acyltransferase. cDNA cloning, expression, and localization to chromosome 9q34.3.
AuthorsEberhardt C, Gray PW, Tjoelker LW
JournalJ Biol Chem
PubMed ID9242711
Lysophosphatidic acid (1-acyl-sn-glycero-3-phosphate (LPA)) is a phospholipid with diverse biological activities. The mediator serves as an intermediate in membrane phospholipid metabolism but is also produced in acute settings by activated platelets. LPA is converted to phosphatidic acid, itself a lipid mediator, by an LPA acyltransferase (LPAAT). A human expressed sequence ... More
NOEY2 (ARHI), an imprinted putative tumor suppressor gene in ovarian and breast carcinomas.
AuthorsYu Y, Xu F, Peng H, Fang X, Zhao S, Li Y, Cuevas B, Kuo WL, Gray JW, Siciliano M, Mills GB, Bast RC Jr
JournalProc Natl Acad Sci U S A
PubMed ID9874798
Using differential display PCR, we have identified a gene [NOEY2, ARHI (designation by the Human Gene Nomenclature Committee)] with high homology to ras and rap that is expressed consistently in normal ovarian and breast epithelial cells but not in ovarian and breast cancers. Reexpression of NOEY2 through transfection suppresses clonogenic ... More
Suppression of apoptosis by cyclophilin D via stabilization of hexokinase II mitochondrial binding in cancer cells.
AuthorsMachida K, Ohta Y, Osada H,
JournalJ Biol Chem
PubMed ID16551620
The permeability transition pore is involved in the mitochondrial pathway of apoptosis. Cyclophilin D, a pore component, has catalytic activity as a peptidyl prolyl cis, trans-isomerase (PPIase), which is essential to the pore opening. It has been reported that cyclophilin D overexpression suppresses apoptosis in cancer cells. To clarify the ... More
A beta-1,3-N-acetylglucosaminyltransferase with poly-N- acetyllactosamine synthase activity is structurally related to beta-1,3- galactosyltransferases.
AuthorsZhou D, Dinter A, Gutierrez Gallego R, Kamerling JP, Vliegenthart JF, Berger EG, Hennet T
JournalProc Natl Acad Sci U S A
PubMed ID9892646
Human and mouse cDNAs encoding a new beta-1, 3-N- acetylglucosaminyltransferase (beta3GnT) have been isolated from fetal and newborn brain libraries. The human and mouse cDNAs included ORFs coding for predicted type II transmembrane polypeptides of 329 and 325 aa, respectively. The human and mouse beta3GnT homologues shared 90% similarity. The ... More
Functional role of p35srj, a novel p300/CBP binding protein, during transactivation by HIF-1.
AuthorsBhattacharya S, Michels CL, Leung MK, Arany ZP, Kung AL, Livingston DM
JournalGenes Dev
PubMed ID9887100
Recruitment of p300/CBP by the hypoxia-inducible factor, HIF-1, is essential for the transcriptional response to hypoxia and requires an interaction between the p300/CBP CH1 region and HIF-1alpha. A new p300- CH1 interacting protein, p35srj, has been identified and cloned. p35srj is an alternatively spliced isoform of MRG1, a human protein ... More
A functional variant of the adipocyte glycerol channel aquaporin 7 gene is associated with obesity and related metabolic abnormalities.
AuthorsPrudente S, Flex E, Morini E, Turchi F, Capponi D, De Cosmo S, Tassi V, Guida V, Avogaro A, Folli F, Maiani F, Frittitta L, Dallapiccola B, Trischitta V,
JournalDiabetes
PubMed ID17351148
Aquaporin 7 (AQP7), the gateway protein controlling glycerol release, has recently emerged as a modulator of adipocyte metabolism. AQP7 knockout mice develop obesity and hyperglycemia. The contribution of AQP7 to these abnormalities in humans is unknown. We examined whether common single nucleotide polymorphisms (SNPs) in the AQP7 gene modulate the ... More
Diverse trafficking patterns due to multiple traffic motifs in g protein-activated inwardly rectifying potassium channels from brain and heart.
Authors Ma Dzwokai; Zerangue Noa; Raab-Graham Kimberly; Fried Sharon R; Jan Yuh Nung; Jan Lily Yeh;
JournalNeuron
PubMed ID11879649
G protein-activated inwardly rectifying potassium channels (Kir3, GIRK) provide an important mechanism for neurotransmitter regulation of membrane excitability. GIRK channels are tetramers containing various combinations of Kir3 subunits (Kir3.1--Kir3.4). We find that different combinations of Kir3 subunits exhibit a surprisingly complex spectrum of trafficking phenotypes. Kir3.2 and Kir3.4, but not ... More
Functional consequence of targeting protein kinase B/Akt to GLUT4 vesicles.
We have investigated the role of protein kinase B (Akt) in the insulin-stimulated translocation of vesicles containing the insulin-responsive isoform of glucose transporter (GLUT4) to the plasma membrane of adipocytes. Previous reports have suggested that protein kinase B can bind to intracellular GLUT4 vesicles in an insulin-dependent manner, but the ... More
Mouse very long-chain acyl-CoA synthetase in X-linked adrenoleukodystrophy.
Authors Heinzer Ann K; Kemp Stephan; Lu Jyh-Feng; Watkins Paul A; Smith Kirby D;
JournalJ Biol Chem
PubMed ID12048192
X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder characterized by accumulation of very long-chain fatty acids (VLCFA). This accumulation has been attributed to decreased VLCFA beta-oxidation and peroxisomal very long-chain acyl-CoA synthetase (VLCS) activity. The X-ALD gene, ABCD1, encodes a peroxisomal membrane ATP binding cassette transporter, ALDP, that is hypothesized to ... More
Ganglioside modulation regulates epithelial cell adhesion and spreading via ganglioside-specific effects on signaling.
Authors Wang Xiao-Qi; Sun Ping; Paller Amy S;
JournalJ Biol Chem
PubMed ID12183467
Gangliosides are implicated in regulating cell adhesion and migration on fibronectin by binding with the alpha(5) subunit of alpha(5)beta(1) integrin. However, the effects of gangliosides on cell spreading and related signaling pathways are unknown. Increases in gangliosides GT1b and GD3 inhibited spreading on fibronectin, concurrent with inhibition of Src and ... More