Abstract:
:SLP-76 is an adapter protein required for T-cell receptor (TCR) signaling. In particular, TCR-induced tyrosine phosphorylation and activation of phospholipase C-gamma1 (PLC-gamma1), and the resultant TCR-inducible gene expression, depend on SLP-76. Nonetheless, the mechanisms by which SLP-76 mediates PLC-gamma1 activation are not well understood. We now demonstrate that SLP-76 directly interacts with the Src homology 3 (SH3) domain of PLC-gamma1. Structure-function analysis of SLP-76 revealed that each of the previously defined protein-protein interaction domains can be individually deleted without completely disrupting SLP-76 function. Additional deletion mutations revealed a new, 67-amino-acid functional domain within the proline-rich region of SLP-76, which we have termed the P-1 domain. The P-1 domain mediates a constitutive interaction of SLP-76 with the SH3 domain of PLC-gamma1 and is required for TCR-mediated activation of Erk, PLC-gamma1, and NFAT (nuclear factor of activated T cells). The adjacent Gads-binding domain of SLP-76, also within the proline-rich region, mediates inducible recruitment of SLP-76 to a PLC-gamma1-containing complex via the recruitment of both PLC-gamma1 and Gads to another cell-type-specific adapter, LAT. Thus, TCR-induced activation of PLC-gamma1 entails the binding of PLC-gamma1 to both LAT and SLP-76, a finding that may underlie the requirement for both LAT and SLP-76 to mediate the optimal activation of PLC-gamma1.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Yablonski D,Kadlecek T,Weiss Adoi
10.1128/MCB.21.13.4208-4218.2001subject
Has Abstractpub_date
2001-07-01 00:00:00pages
4208-18issue
13eissn
0270-7306issn
1098-5549journal_volume
21pub_type
杂志文章abstract::The level of phosphotyrosine in vinculin was determined in chicken embryo fibroblasts transformed by various strains of avian sarcoma virus. As previously reported (Sefton et al., Cell 24:165-174, 1981), vinculin was phosphorylated at tyrosine residues in most cultures examined, but the level varied greatly and no det...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.1.263
更新日期:1985-01-01 00:00:00
abstract::The pocket protein family of tumor suppressors, and Rb specifically, have been implicated as controlling terminal differentiation in many tissues, including the heart. To establish the biological functions of Rb in the heart and overcome the early lethality caused by germ line deletion of Rb, we used a Cre/loxP system...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.6.2486-2497.2005
更新日期:2005-03-01 00:00:00
abstract::Recent research has identified critical roles for microRNAs in a large number of cellular processes, including tumorigenic transformation. While significant progress has been made towards understanding the mechanisms of gene regulation by microRNAs, much less is known about factors affecting the expression of these no...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01395-06
更新日期:2007-03-01 00:00:00
abstract::Peroxisomal PTS2-dependent matrix protein import starts with the recognition of the PTS2 targeting signal by the import receptor Pex7p. Subsequently, the formed Pex7p/cargo complex is transported from the cytosol to the peroxisomal docking complex, consisting of Pex13p and Pex14p. In Saccharomyces cerevisiae, the latt...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.17.6056-6069.2002
更新日期:2002-09-01 00:00:00
abstract::ADAR2 is a double-stranded-RNA-specific adenosine deaminase involved in the editing of mammalian RNAs by the site-selective conversion of adenosine to inosine. Previous studies from our laboratory have demonstrated that ADAR2 can modify its own pre-mRNA to create a proximal 3' splice site containing a noncanonical ade...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.26.2.480-488.2006
更新日期:2006-01-01 00:00:00
abstract::To distinguish among possible mechanisms of repair of a double-strand break (DSB) by gene conversion in budding yeast, Saccharomyces cerevisiae, we employed isotope density transfer to analyze budding yeast mating type (MAT) gene switching in G2/M-arrested cells. Both of the newly synthesized DNA strands created durin...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01654-06
更新日期:2006-12-01 00:00:00
abstract::Human La protein has been shown to serve as a transcription factor for RNA polymerase III (pol III) by facilitating transcription termination and recycling of transcription complexes. In addition, La binds to the 3' oligo(U) ends common to all nascent pol III transcripts, and in the case of B1-Alu RNA, protects it fro...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.10.5823
更新日期:1997-10-01 00:00:00
abstract::Phosphorylation of eukaryotic initiation factor 2 alpha (eIF-2 alpha) is typically associated with stress responses and causes a reduction in protein synthesis. However, we found high phosphorylated eIF-2 alpha (eIF-2 alpha[P]) levels in nonstressed pancreata of mice. Administration of glucose stimulated a rapid depho...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.11.3864-3874.2002
更新日期:2002-06-01 00:00:00
abstract::Acidic fibroblast growth factor (FGF) and related family members regulate differentiation in organisms as diverse as Xenopus laevis and mammals. We utilized a well-characterized model of myogenic development to directly assess the importance of endogenously produced FGF in controlling differentiation. A role for endog...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.6.4244
更新日期:1994-06-01 00:00:00
abstract::Though widely recognized in higher eukaryotes, the regulation of Saccharomyces cerevisiae genes transcribed by RNA polymerase II by proteins that bind within the coding sequence remains largely speculative. We have shown for the LPD1 gene, encoding lipoamide dehydrogenase, that the coding sequence between +13 and +469...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.1.214
更新日期:1994-01-01 00:00:00
abstract::Determining the functions of novel genes implicated in cell survival is directly relevant to our understanding of mammalian development and carcinogenesis. ARS2 is an evolutionarily conserved gene that confers arsenite resistance on arsenite-sensitive Chinese hamster ovary cells. Little is known regarding the function...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01565-07
更新日期:2008-03-01 00:00:00
abstract::The coordinated expression of CD4 and CD8 during T-cell development is tightly coupled with the maturation state of the T cell. Additionally, the mutually exclusive expression of these receptors in mature T cells is representative of the functional T-cell subclasses (CD4+ helper T cells versus CD8+ cytotoxic T cells)....
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.10.6452
更新日期:1994-10-01 00:00:00
abstract::The RAD1 gene of Saccharomyces cerevisiae is required for the incision step of excision repair of damaged DNA. In this paper, we report our observations on the effect of the RAD1 gene on genetic recombination. Mitotic intrachromosomal and interchromosomal recombination in RAD+, rad1, rad52, and other rad mutant strain...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.9.3619
更新日期:1988-09-01 00:00:00
abstract::To determine the types of alterations in gene structure induced by DNA-alkylating agents, we analyzed the restriction enzyme cleavage patterns of adenine phosphoribosyltransferase gene sequences in mutant strains of Chinese hamster ovary cells deficient in this enzyme. Base pair changes as detected by loss of restrict...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.2.11.1459
更新日期:1982-11-01 00:00:00
abstract::The full-length normal and T24 mutant human H-ras proteins and two truncated derivatives of the T24 mutant were expressed efficiently in Escherichia coli. The proteins accumulated to 1 to 5% of total cellular protein, and each was specifically recognized by anti-ras monoclonal antibodies. The two full-length proteins ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.5.1015
更新日期:1985-05-01 00:00:00
abstract::Throughout life, intestinal Lgr5+ stem cells give rise to proliferating transient amplifying cells in crypts, which subsequently differentiate into one of the five main cell types and migrate along the crypt-villus axis. These dynamic processes are coordinated by a relatively small number of evolutionarily conserved s...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.06288-11
更新日期:2012-05-01 00:00:00
abstract::The v-myb oncogene of avian myeloblastosis virus causes acute myelomonocytic leukemia in chickens and transforms avian myeloid cells in vitro. Its protein product p48v-myb is a nuclear, sequence-specific, DNA-binding protein which activates gene expression in transient DNA transfection studies. To investigate the rela...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.6.2591
更新日期:1990-06-01 00:00:00
abstract::Exposure of monocytic cells to bacterial lipopolysaccharide (LPS) activates the NF-kappa B/Rel family of proteins and leads to the rapid induction of inflammatory gene products, including tissue factor (TF). TF is the primary cellular initiator of the coagulation protease cascades. Here we report the characterization ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.6.3772
更新日期:1994-06-01 00:00:00
abstract::Topoisomerase I cleavage complexes can be induced by a variety of DNA damages and by the anticancer drug camptothecin. We have developed a ligation-mediated PCR (LM-PCR) assay to analyze replication-mediated DNA double-strand breaks induced by topoisomerase I cleavage complexes in human colon carcinoma HT29 cells at t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.11.3977-3987.2000
更新日期:2000-06-01 00:00:00
abstract::Eukaryotic chromosomes are organized into domains of activity for both transcription and DNA replication. Transcriptional "border," or "insulator," elements have been implicated in mediating the organization of transcriptional domains. However, the DNA sequence elements which might demarcate domains of DNA replication...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.4.2202
更新日期:1997-04-01 00:00:00
abstract::Phosphorylation is one of the key mechanisms that regulate centrosome biogenesis, spindle assembly, and cell cycle progression. However, little is known about centrosome-specific phosphorylation sites and their functional relevance. Here, we identified phosphoproteins of intact Drosophila melanogaster centrosomes and ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00814-12
更新日期:2012-09-01 00:00:00
abstract::Retinoid X receptors (RXR) have been identified as common subunits in the regulation of multiple hormonal signaling pathways. Using circular permutation and phasing analysis of specific response elements, we present evidence that RXR-retinoic acid receptor and RXR-thyroid hormone receptor heterodimer or RXR-RXR homodi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.10.6509
更新日期:1993-10-01 00:00:00
abstract::Revertants were selected from aryl hydrocarbon hydroxylase (AHH)-deficient recessive mutants belonging to three complementation groups and from a dominant mutant of the Hepa-1 cell line. The recessive mutants had low spontaneous reversion frequencies (less than 4 X 10(-7] that were increased by mutagenesis. The majori...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.8.1597
更新日期:1984-08-01 00:00:00
abstract::Protein tyrosine kinases activate the STAT (signal transducer and activator of transcription) signaling pathway, which can play essential roles in cell differentiation, cell cycle control, and development. However, the potential role of the STAT signaling pathway in the induction of apoptosis remains unexplored. Here ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.9.5328
更新日期:1997-09-01 00:00:00
abstract::A potential p120 GTPase-activating protein (RasGAP) effector, G3BP (RasGAP Src homology 3 [SH3] binding protein), was previously identified based on its ability to bind the SH3 domain of RasGAP. Here we show that G3BP colocalizes and physically interacts with RasGAP at the plasma membrane of serum-stimulated but not q...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.7.3956
更新日期:1998-07-01 00:00:00
abstract::TBC (Tre-2/Bub2/Cdc16) domains are predicted to encode GTPase-activating proteins (GAPs) for Rab family G proteins. While approximately 50 TBC proteins are predicted to exist in humans, little is known about their substrate specificity. Here we show that TRE17 (also called Tre-2 and USP6), a founding member of the TBC...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.22.9752-9762.2004
更新日期:2004-11-01 00:00:00
abstract::Following a proliferative phase of variable duration, most normal somatic cells enter a growth arrest state known as replicative senescence. In addition to telomere shortening, a variety of environmental insults and signaling imbalances can elicit phenotypes closely resembling senescence. We used p53(-/-) and p21(-/-)...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.20.6748-6757.2001
更新日期:2001-10-01 00:00:00
abstract::A region of the Saccharomyces cerevisiae mitochondrial cytochrome b gene encompassing the entire terminal intron plus flanking exonic sequences has been cloned in an SP6 vector. A runoff transcript prepared from this construct as well as the native cytochrome b pre-mRNA containing the terminal intervening sequence wer...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.7.2545
更新日期:1987-07-01 00:00:00
abstract::The Saccharomyces cerevisiae SWI4 gene encodes an essential transcription factor which controls gene expression at the G1/S transition of the cell cycle. SWI4 transcription itself is cell cycle regulated, and this periodicity is crucial for the normal cell cycle regulation of HO and at least two of the G1 cyclins. Sin...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.6.3792
更新日期:1993-06-01 00:00:00
abstract::The reciprocal expression of GATA-1 and GATA-2 during hematopoiesis is an important determinant of red blood cell development. Whereas Gata2 is preferentially transcribed early in hematopoiesis, elevated GATA-1 levels result in GATA-1 occupancy at sites upstream of the Gata2 locus and transcriptional repression. GATA-...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01033-06
更新日期:2006-10-01 00:00:00