Identification of a phospholipase C-gamma1 (PLC-gamma1) SH3 domain-binding site in SLP-76 required for T-cell receptor-mediated activation of PLC-gamma1 and NFAT.

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 Biol

authors

Yablonski D,Kadlecek T,Weiss A

doi

10.1128/MCB.21.13.4208-4218.2001

subject

Has Abstract

pub_date

2001-07-01 00:00:00

pages

4208-18

issue

13

eissn

0270-7306

issn

1098-5549

journal_volume

21

pub_type

杂志文章
  • Increased phosphorylation of tyrosine in vinculin does not occur upon transformation by some avian sarcoma viruses.

    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

    authors: Antler AM,Greenberg ME,Edelman GM,Hanafusa H

    更新日期:1985-01-01 00:00:00

  • Overlapping roles of pocket proteins in the myocardium are unmasked by germ line deletion of p130 plus heart-specific deletion of Rb.

    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

    authors: MacLellan WR,Garcia A,Oh H,Frenkel P,Jordan MC,Roos KP,Schneider MD

    更新日期:2005-03-01 00:00:00

  • A microRNA signature of hypoxia.

    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

    authors: Kulshreshtha R,Ferracin M,Wojcik SE,Garzon R,Alder H,Agosto-Perez FJ,Davuluri R,Liu CG,Croce CM,Negrini M,Calin GA,Ivan M

    更新日期:2007-03-01 00:00:00

  • Interactions of Pex7p and Pex18p/Pex21p with the peroxisomal docking machinery: implications for the first steps in PTS2 protein import.

    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

    authors: Stein K,Schell-Steven A,Erdmann R,Rottensteiner H

    更新日期:2002-09-01 00:00:00

  • Altered RNA editing in mice lacking ADAR2 autoregulation.

    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

    authors: Feng Y,Sansam CL,Singh M,Emeson RB

    更新日期:2006-01-01 00:00:00

  • Conservative inheritance of newly synthesized DNA in double-strand break-induced gene conversion.

    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

    authors: Ira G,Satory D,Haber JE

    更新日期:2006-12-01 00:00:00

  • A carboxy-terminal basic region controls RNA polymerase III transcription factor activity of human La protein.

    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

    authors: Goodier JL,Fan H,Maraia RJ

    更新日期:1997-10-01 00:00:00

  • The PERK eukaryotic initiation factor 2 alpha kinase is required for the development of the skeletal system, postnatal growth, and the function and viability of the pancreas.

    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

    authors: Zhang P,McGrath B,Li S,Frank A,Zambito F,Reinert J,Gannon M,Ma K,McNaughton K,Cavener DR

    更新日期:2002-06-01 00:00:00

  • Myogenic differentiation triggered by antisense acidic fibroblast growth factor RNA.

    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

    authors: Fox JC,Hsu AY,Swain JL

    更新日期:1994-06-01 00:00:00

  • Yeast intragenic transcriptional control: activation and repression sites within the coding region of the Saccharomyces cerevisiae LPD1 gene.

    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

    authors: Sinclair DA,Kornfeld GD,Dawes IW

    更新日期:1994-01-01 00:00:00

  • ARS2 is a conserved eukaryotic gene essential for early mammalian development.

    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

    authors: Wilson MD,Wang D,Wagner R,Breyssens H,Gertsenstein M,Lobe C,Lu X,Nagy A,Burke RD,Koop BF,Howard PL

    更新日期:2008-03-01 00:00:00

  • Elf-1 binds to a critical element in a second CD4 enhancer.

    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

    authors: Wurster AL,Siu G,Leiden JM,Hedrick SM

    更新日期:1994-10-01 00:00:00

  • RAD1, an excision repair gene of Saccharomyces cerevisiae, is also involved in recombination.

    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

    authors: Schiestl RH,Prakash S

    更新日期:1988-09-01 00:00:00

  • Alterations of gene structure in ethyl methane sulfonate-induced mutants of mammalian cells.

    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

    authors: Meuth M,Arrand JE

    更新日期:1982-11-01 00:00:00

  • Purification and characterization of human H-ras proteins expressed in Escherichia coli.

    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

    authors: Gross M,Sweet RW,Sathe G,Yokoyama S,Fasano O,Goldfarb M,Wigler M,Rosenberg M

    更新日期:1985-05-01 00:00:00

  • A critical role for the Wnt effector Tcf4 in adult intestinal homeostatic self-renewal.

    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

    authors: van Es JH,Haegebarth A,Kujala P,Itzkovitz S,Koo BK,Boj SF,Korving J,van den Born M,van Oudenaarden A,Robine S,Clevers H

    更新日期:2012-05-01 00:00:00

  • Transformation by v-myb correlates with trans-activation of gene expression.

    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

    authors: Lane T,Ibanez C,Garcia A,Graf T,Lipsick J

    更新日期:1990-06-01 00:00:00

  • Lipopolysaccharide induction of tissue factor gene expression in monocytic cells is mediated by binding of c-Rel/p65 heterodimers to a kappa B-like site.

    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

    authors: Oeth PA,Parry GC,Kunsch C,Nantermet P,Rosen CA,Mackman N

    更新日期:1994-06-01 00:00:00

  • Conversion of topoisomerase I cleavage complexes on the leading strand of ribosomal DNA into 5'-phosphorylated DNA double-strand breaks by replication runoff.

    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

    authors: Strumberg D,Pilon AA,Smith M,Hickey R,Malkas L,Pommier Y

    更新日期:2000-06-01 00:00:00

  • A transcriptional insulator element, the su(Hw) binding site, protects a chromosomal DNA replication origin from position effects.

    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

    authors: Lu L,Tower J

    更新日期:1997-04-01 00:00:00

  • Functional analysis of centrosomal kinase substrates in Drosophila melanogaster reveals a new function of the nuclear envelope component otefin in cell cycle progression.

    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

    authors: Habermann K,Mirgorodskaya E,Gobom J,Lehmann V,Müller H,Blümlein K,Deery MJ,Czogiel I,Erdmann C,Ralser M,von Kries JP,Lange BM

    更新日期:2012-09-01 00:00:00

  • DNA bending by retinoid X receptor-containing retinoid and thyroid hormone receptor complexes.

    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

    authors: Lu XP,Eberhardt NL,Pfahl M

    更新日期:1993-10-01 00:00:00

  • Isolation and characterization of revertants from four different classes of aryl hydrocarbon hydroxylase-deficient hepa-1 mutants.

    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

    authors: Van Gurp JR,Hankinson O

    更新日期:1984-08-01 00:00:00

  • Activation of the STAT signaling pathway can cause expression of caspase 1 and apoptosis.

    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

    authors: Chin YE,Kitagawa M,Kuida K,Flavell RA,Fu XY

    更新日期:1997-09-01 00:00:00

  • A novel phosphorylation-dependent RNase activity of GAP-SH3 binding protein: a potential link between signal transduction and RNA stability.

    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

    authors: Gallouzi IE,Parker F,Chebli K,Maurier F,Labourier E,Barlat I,Capony JP,Tocque B,Tazi J

    更新日期:1998-07-01 00:00:00

  • The TBC (Tre-2/Bub2/Cdc16) domain protein TRE17 regulates plasma membrane-endosomal trafficking through activation of Arf6.

    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

    authors: Martinu L,Masuda-Robens JM,Robertson SE,Santy LC,Casanova JE,Chou MM

    更新日期:2004-11-01 00:00:00

  • Role of p14(ARF) in replicative and induced senescence of human fibroblasts.

    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

    authors: Wei W,Hemmer RM,Sedivy JM

    更新日期:2001-10-01 00:00:00

  • In vitro splicing of the terminal intervening sequence of Saccharomyces cerevisiae cytochrome b pre-mRNA.

    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

    authors: Gampel A,Tzagoloff A

    更新日期:1987-07-01 00:00:00

  • Multiple SWI6-dependent cis-acting elements control SWI4 transcription through the cell cycle.

    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

    authors: Foster R,Mikesell GE,Breeden L

    更新日期:1993-06-01 00:00:00

  • Distinct functions of dispersed GATA factor complexes at an endogenous gene locus.

    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

    authors: Grass JA,Jing H,Kim SI,Martowicz ML,Pal S,Blobel GA,Bresnick EH

    更新日期:2006-10-01 00:00:00