Abstract:
:We report the isolation and molecular characterization of the mouse grb2 gene. The product of this gene, the Grb2 protein, is highly related to the Caenorhabditis elegans sem-5 gene product and the human GRB2 protein and displays the same SH3-SH2-SH3 structural motifs. In situ hybridization studies revealed that the mouse grb2 gene is widely expressed throughout embryonic development (E9.5 to P0). However, grb2 transcripts are not uniformly distributed, and in certain tissues (e.g., thymus) they appear to be regulated during development. Recent genetic and biochemical evidence has implicated the Grb2 protein in the signaling pathways that link cell surface tyrosine kinase receptors with Ras. We have investigated the association of the Grb2 protein with epidermal growth factor (EGF) and nerve growth factor (NGF) receptors in PC12 pheochromocytoma cells. EGF treatment of PC12 cells results in the rapid association of Grb2 with the activated EGF receptors, an interaction mediated by the Grb2 SH2 domain. However, Grb2 does not bind to NGF-activated Trk receptors. Mitogenic signaling of NGF in NIH 3T3 cells ectopically expressing Trk receptors also takes place without detectable association between Grb2 and Trk. These results suggest that whereas EGF and NGF can activate the Ras signaling pathway in PC12 cells, only the EGF receptor is likely to do so through a direct interaction with Grb2. Finally, binding studies with glutathione S-transferase fusion proteins indicate that Grb2 binds two distinct subsets of proteins which are individually recognized by its SH2 and SH3 domains. These observations add further support to the concept that Grb2 is a modular adaptor protein.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Suen KL,Bustelo XR,Pawson T,Barbacid Mdoi
10.1128/mcb.13.9.5500subject
Has Abstractpub_date
1993-09-01 00:00:00pages
5500-12issue
9eissn
0270-7306issn
1098-5549journal_volume
13pub_type
杂志文章abstract::Epidermal growth factor (EGF) receptor (EGFR) has been implicated in tumor development and invasion. Dimerization and autophosphorylation of EGFR are the critical events for EGFR activation. However, the regulation of EGF-dependent and EGF-independent dimerization and phosphorylation of EGFR has not been fully underst...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00758-14
更新日期:2014-10-01 00:00:00
abstract::The erbB-2 gene product, gp185erbB-2, unlike the structurally related epidermal growth factor (EGF) receptor (EGFR), exhibits constitutive kinase and transforming activity. We used a chimeric EGFR/erbB-2 expression vector to compare the mitogenic signaling pathway of the erbB-2 kinase with that of the EGFR, at similar...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.4.2040
更新日期:1991-04-01 00:00:00
abstract::Hepatitis C virus (HCV) NS5B protein is a membrane-associated phosphoprotein that possesses an RNA-dependent RNA polymerase activity. We recently reported that NS5A protein interacts with TRAF2 and modulates tumor necrosis factor alpha (TNF-alpha)-induced NF-kappaB and Jun N-terminal protein kinase (JNK). Since NS5A a...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.26.8.3048-3059.2006
更新日期:2006-04-01 00:00:00
abstract::Previously, we identified the E3 ubiquitin ligase Idol (inducible degrader of the low-density lipoprotein [LDL] receptor [LDLR]) as a posttranscriptional regulator of the LDLR pathway. Idol stimulates LDLR degradation through ubiquitination of its C-terminal domain, thereby limiting cholesterol uptake. Here we report ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01469-10
更新日期:2011-05-01 00:00:00
abstract::Mrc1 is a conserved checkpoint mediator protein that transduces the replication stress signal to the downstream effector kinase. The loss of mrc1 checkpoint activity results in the aberrant activation of late/dormant origins in the presence of hydroxyurea. Mrc1 was also suggested to regulate orders of early origin fir...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00355-16
更新日期:2017-03-17 00:00:00
abstract::There are three mechanisms of transcriptional repression in eukaryotes. The first is quenching, whereby repressors and activators co-occupy closely linked sites and then the repressor inhibits adjacent activators. The second is direct repression, in which repressors block the function of the core transcription complex...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.11.3990-3999.2003
更新日期:2003-06-01 00:00:00
abstract::Selective and accurate transcription of purified genes by RNA polymerase II requires multiple factors. The factor designated TFIID was purified extensively from HeLa cell nuclear extracts by using a simple and novel complementation assay. Thus, TFIID was preferentially inactivated by mild heat treatment of a nuclear e...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.10.4028
更新日期:1988-10-01 00:00:00
abstract::The serum response factor (p67SRF) binds to a palindromic sequence in the c-fos serum response element (SRE). A second protein, p62TCF binds in conjunction with p67SRF to form a ternary complex, and it is through this complex that growth factor-induced transcriptional activation of c-fos is thought to take place. A 90...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.1.123
更新日期:1993-01-01 00:00:00
abstract::Although largely involved in innate and adaptive immunity, NF-kappa B plays an important role in vertebrate development. In chicks, the inactivation of the NF-kappa B pathway induces functional alterations of the apical ectodermal ridge, which mediates limb outgrowth. In mice, the complete absence of NF-kappa B activi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.12.5257-5268.2004
更新日期:2004-06-01 00:00:00
abstract::To interrogate genes essential for cell growth, proliferation and survival in human cells, we carried out a genome-wide clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 screen in a B-cell lymphoma line using a custom extended-knockout (EKO) library of 278,754 single-guide RNAs (sgRNAs) that targe...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00302-17
更新日期:2017-12-13 00:00:00
abstract::Endonuclease decay of nonsense-containing beta-globin mRNA in erythroid cells generates 5'-truncated products that were reported previously to have a cap or caplike structure. We confirmed that this 5' modification is indistinguishable from the cap on full-length mRNA, and Western blotting, immunoprecipitation, and ac...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01325-08
更新日期:2009-04-01 00:00:00
abstract::An interferon-alpha-like sequence was isolated from a human genomic library by hybridization with a 15-base oligonucleotide. The sequence also showed homology to alpha-interferon and was most closely related to the leukocyte interferon-M gene fragment. The original isolate cross-hybridized to a family of sequences, 10...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.3.510
更新日期:1985-03-01 00:00:00
abstract::FUD6, a nonphotosynthetic mutant of Chlamydomonas reinhardtii, was previously found to be deficient in the synthesis of subunit IV of the cytochrome b6/f complex, the chloroplast petD gene product (C. Lemaire, J. Girard-Bascou, F.-A. Wollman, and P. Bennoun, Biochim. Biophys. Acta 851:229-238, 1986). The lesion in FUD...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.9.6171
更新日期:1994-09-01 00:00:00
abstract::An accumulation in cells of unfolded proteins is believed to be the common signal triggering the induction of heat shock proteins (hsps). Accordingly, in Saccharomyces cerevisiae, inhibition of protein breakdown at 30 degrees C with the proteasome inhibitor MG132 caused a coordinate induction of many heat shock protei...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.1.30
更新日期:1998-01-01 00:00:00
abstract::Interleukin 4 (IL-4), an immunoregulatory cytokine, is produced only by a subset of activated T cells and cells of the mast cell-basophil lineage. The production of IL-4 by mast cells likely represents a significant source of this protein in local immune-inflammatory responses in the skin, brain, gastrointestinal, and...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.1.228
更新日期:1996-01-01 00:00:00
abstract::The dorsal protein (DL) regulates the transcriptional activity of several genes that determine cell fate along the dorsoventral axis of the Drosophila melanogaster embryo. DL is present at high levels in ventral nuclei, where it activates some genes (twi and sna) and represses others (zen, dpp, and tld). DL shows homo...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.1.713
更新日期:1994-01-01 00:00:00
abstract::Unique single-stranded regions of simian virus 40 DNA, phage M13 virion DNA, and several homopolymers were used as templates for the synthesis of (p)ppRNA-DNA chains by CV-1 cell DNA primase-DNA polymerase alpha. Intact RNA primers, specifically labeled with an RNA capping enzyme, were typically 6 to 8 ribonucleotides...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.5.1170
更新日期:1985-05-01 00:00:00
abstract::To evaluate the role of mitogen-activated protein (MAP) kinase and other signaling pathways in neuronal cell differentiation by basic fibroblast-derived growth factor (bFGF), we used a conditionally immortalized cell line from rat hippocampal neurons (H19-7). Previous studies have shown that activation of MAP kinase k...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.8.4633
更新日期:1997-08-01 00:00:00
abstract::mRNA deadenylation is a key process in the regulation of translation and mRNA turnover. In Saccharomyces cerevisiae, deadenylation is primarily carried out by the Ccr4p and Caf1p/Pop2p subunits of the Ccr4-Not complex, which is conserved in eukaryotes including humans. Here we have identified an unconventional human C...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01483-06
更新日期:2007-03-01 00:00:00
abstract::The RBP-J/Su(H) DNA-binding protein plays a key role in transcriptional regulation by targeting Epstein-Barr virus nuclear antigen 2 (EBNA2) and the intracellular portions of Notch receptors to specific promoters. Using the yeast two-hybrid system, we isolated a LIM-only protein, KyoT, which physically interacts with ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.1.644
更新日期:1998-01-01 00:00:00
abstract::Cytosine methylation at CpG dinucleotides is thought to cause more than one-third of all transition mutations responsible for human genetic diseases and cancer. We investigated the methylation status of the CpG dinucleotide at codon 248 in exon 7 of the p53 gene because this codon is a hot spot for inactivating mutati...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.6.4225
更新日期:1994-06-01 00:00:00
abstract::Although an F-box protein, Mdm30, is found to regulate ubiquitylation of the Sub2 component of TREX (transcription-export) complex for proteasomal degradation in stimulation of mRNA export, it remains unknown whether such ubiquitin-proteasome system (UPS) regulation of Sub2 occurs cotranscriptionally via its interacti...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00570-19
更新日期:2020-03-16 00:00:00
abstract::The GTPase-activating protein (GAP) stimulates the GTPase reaction of p21 by 5 orders of magnitude such that the kcat of the reaction is increased to 19 s-1. Mutations of residues in loop L1 (Gly-12 and Gly-13), in loop L2 (Thr-35 and Asp-38), and in loop L4 (Gln-61 and Glu-63) influence the reaction in different ways...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.5.2050
更新日期:1992-05-01 00:00:00
abstract::Saccharomyces cerevisiae dbf4 and cdc7 cell cycle mutants block initiation of DNA synthesis (i.e., are iDS mutants) at 37 degrees C and arrest the cell cycle with a 1C DNA content. Surprisingly, certain dbf4 and cdc7 strains divide their chromatin at 37 degrees C. We found that the activation of the Cdc28 mitotic prot...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.10.5312
更新日期:1995-10-01 00:00:00
abstract::The interleukin enhancer binding factors ILF2 (NF45) and ILF3 (NF90/NF110) have been implicated in various cellular pathways, such as transcription, microRNA (miRNA) processing, DNA repair, and translation, in mammalian cells. Using tandem affinity purification, we identified human NF45 and NF90 as components of precu...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00306-15
更新日期:2015-10-01 00:00:00
abstract::NIH3T3 cells transformed by mouse Int-2/Fgf-3 cDNA express a series of Int-2-related products representing discrete stages of processing and glycosylation. We confirm that in at least two highly transformed clonal lines, Int-2 products acquire further modifications and are efficiently secreted into the culture medium....
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.12.5929
更新日期:1991-12-01 00:00:00
abstract::Determining the roles of Rel/NF-kappaB transcription factors in mouse skin development with loss-of-function mutants has been limited by redundancy among these proteins and by embryonic lethality associated with the absence of RelA. Using mice lacking RelA and c-rel, which survive throughout embryogenesis on a tumor n...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.13.5733-5745.2004
更新日期:2004-07-01 00:00:00
abstract::In Chlamydomonas reinhardi the chloroplast DNA (ch;DNA) of mating type plus cells undergoes cyclical methylation and demethylation during the life cycle. Methylation occurs during gametogenesis, and fully differentiated gametes can be dedifferentiated back to vegetative cells which contain nonmethylated chlDNA by the ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.10.2103
更新日期:1984-10-01 00:00:00
abstract::The single-copy gene encoding the alpha subunit of glycoprotein hormones is expressed in the pituitaries of all mammals and in the placentas of only primates and horses. We have systematically analyzed the promoter-regulatory elements of the human and bovine alpha-subunit genes to elucidate the molecular mechanisms un...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.11.5113
更新日期:1989-11-01 00:00:00
abstract::In self-fertile strains of the fission yeast Schizosaccharomyces pombe, nitrogen starvation initiates a program of sexual development in which cells express mating pheromones and receptors, arrest cell cycle progression in G1, and conjugate. This process is dependent on Rum1, an inhibitor of the Cdc2-Cdc13 and Cdc2-Ci...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.1.10
更新日期:1997-01-01 00:00:00