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rdf:type |
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lifeskim:mentions |
umls-concept:C0004083,
umls-concept:C0031671,
umls-concept:C0033684,
umls-concept:C0039194,
umls-concept:C0044602,
umls-concept:C0217093,
umls-concept:C1333707,
umls-concept:C1418576,
umls-concept:C1418577,
umls-concept:C1423080,
umls-concept:C1423613,
umls-concept:C1711351
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pubmed:issue |
34
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pubmed:dateCreated |
1995-9-28
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pubmed:abstractText |
Tyrosine phosphorylation of cellular proteins is an early and an essential step in T cell receptor-mediated lymphocyte activation. Tyrosine phosphorylation of transmembrane receptor chains (such as zeta and CD3 chains) and membrane-associated proteins provides docking sites for SH2 domains of adaptor proteins and signaling enzymes, resulting in their recruitment in the vicinity of activated receptors. pp36/38 is a prominent substrate of early tyrosine phosphorylation upon stimulation through the T cell receptor. The tyrosine-phosphorylated form of pp36/38 is membrane-associated and directly interacts with phospholipase C-gamma 1 and Grb2, providing one mechanism to recruit downstream effectors to the cell membrane. Here, we demonstrate that in Jurkat T cells, pp36/38 associates with the p85 subunit of phosphatidylinositol 3-kinase (PI-3-K p85) in an activation-dependent manner. Association of pp36/38 with PI-3-K p85 was confirmed by transfection of a hemagglutinin-tagged p85 alpha cDNA into Jurkat cells followed by anti-hemagglutinin immunoprecipitation. In vitro binding experiments with glutathione S-transferase fusion proteins of PI-3-K p85 demonstrated that the SH2 domains, but not the SH3 domain, mediated binding to pp36/38. This binding was selectively abrogated by phosphopeptides that bind to p85 SH2 domains with high affinity. Filter binding assays demonstrated that association between pp36/38 and PI-3-K p85 SH2 domains was due to direct binding. These results strongly suggest the role of pp36/38 in recruiting PI-3-K to the cell membrane and further support the idea that pp36/38 is a multifunctional docking protein for SH2 domain-containing signaling proteins in T cells.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/GRB2 Adaptor Protein,
http://linkedlifedata.com/resource/pubmed/chemical/GRB2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Grb2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipase C gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases (Alcohol Group...,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Type C Phospholipases,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
25
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pubmed:volume |
270
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
20177-82
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:7544353-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:7544353-Amino Acid Sequence,
pubmed-meshheading:7544353-Animals,
pubmed-meshheading:7544353-Binding Sites,
pubmed-meshheading:7544353-Cell Line,
pubmed-meshheading:7544353-Cell Membrane,
pubmed-meshheading:7544353-Cricetinae,
pubmed-meshheading:7544353-GRB2 Adaptor Protein,
pubmed-meshheading:7544353-Humans,
pubmed-meshheading:7544353-Isoenzymes,
pubmed-meshheading:7544353-Kinetics,
pubmed-meshheading:7544353-Lymphocyte Activation,
pubmed-meshheading:7544353-Mice,
pubmed-meshheading:7544353-Molecular Sequence Data,
pubmed-meshheading:7544353-Molecular Weight,
pubmed-meshheading:7544353-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:7544353-Phospholipase C gamma,
pubmed-meshheading:7544353-Phosphoproteins,
pubmed-meshheading:7544353-Phosphotransferases (Alcohol Group Acceptor),
pubmed-meshheading:7544353-Phosphotyrosine,
pubmed-meshheading:7544353-Protein Conformation,
pubmed-meshheading:7544353-Proteins,
pubmed-meshheading:7544353-Recombinant Fusion Proteins,
pubmed-meshheading:7544353-T-Lymphocytes,
pubmed-meshheading:7544353-Transfection,
pubmed-meshheading:7544353-Type C Phospholipases,
pubmed-meshheading:7544353-Tyrosine
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pubmed:year |
1995
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pubmed:articleTitle |
T cell activation-dependent association between the p85 subunit of the phosphatidylinositol 3-kinase and Grb2/phospholipase C-gamma 1-binding phosphotyrosyl protein pp36/38.
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pubmed:affiliation |
Department of Rheumatology and Immunology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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