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rdf:type |
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lifeskim:mentions |
umls-concept:C0037083,
umls-concept:C0085536,
umls-concept:C0205314,
umls-concept:C0242275,
umls-concept:C0293442,
umls-concept:C0679622,
umls-concept:C1179132,
umls-concept:C1335280,
umls-concept:C1706044,
umls-concept:C1710082,
umls-concept:C1710236
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pubmed:issue |
28
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pubmed:dateCreated |
2004-7-5
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pubmed:abstractText |
The catalytic activity of the Src homology 2 (SH2) domain-containing tyrosine phosphatase, SHP-2, is required for virtually all of its signaling effects. Elucidating the molecular mechanisms of SHP-2 signaling, therefore, rests upon the identification of its target substrates. In this report, we have used SHP-2 substrate-trapping mutants to identify the major vault protein (MVP) as a putative SHP-2 substrate. MVP is the predominant component of vaults that are cytoplasmic ribonucleoprotein complexes of unknown function. We show that MVP is dephosphorylated by SHP-2 in vitro and it forms an enzyme-substrate complex with SHP-2 in vivo. In response to epidermal growth factor (EGF), SHP-2 associates via its SH2 domains with tyrosyl-phosphorylated MVP. MVP also interacts with the activated form of the extracellular-regulated kinases (Erks) in response to EGF and a constitutive complex between tyrosyl-phosphorylated MVP, SHP-2, and the Erks was detected in MCF-7 breast cancer cells. Using MVP-deficient fibroblasts, we demonstrate that MVP cooperates with Ras for optimal EGF-induced Elk-1 activation and is required for cell survival. We propose that MVP functions as a novel scaffold protein for both SHP-2 and Erk. The regulation of MVP tyrosyl phosphorylation by SHP-2 may play an important role in cell survival signaling.
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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/Culture Media, Serum-Free,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ELK1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Elk1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/PTPN11 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ptpn11 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SH2 Domain-Containing Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Vault Ribonucleoprotein Particles,
http://linkedlifedata.com/resource/pubmed/chemical/ets-Domain Protein Elk-1,
http://linkedlifedata.com/resource/pubmed/chemical/major vault protein
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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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 |
9
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
29374-85
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15133037-Amino Acid Sequence,
pubmed-meshheading:15133037-Animals,
pubmed-meshheading:15133037-Cell Line, Tumor,
pubmed-meshheading:15133037-Cell Survival,
pubmed-meshheading:15133037-Cells, Cultured,
pubmed-meshheading:15133037-Culture Media, Serum-Free,
pubmed-meshheading:15133037-DNA-Binding Proteins,
pubmed-meshheading:15133037-Enzyme Activation,
pubmed-meshheading:15133037-Epidermal Growth Factor,
pubmed-meshheading:15133037-Fibroblasts,
pubmed-meshheading:15133037-Humans,
pubmed-meshheading:15133037-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:15133037-Mice,
pubmed-meshheading:15133037-Mitogen-Activated Protein Kinases,
pubmed-meshheading:15133037-Molecular Sequence Data,
pubmed-meshheading:15133037-Phosphorylation,
pubmed-meshheading:15133037-Protein Structure, Tertiary,
pubmed-meshheading:15133037-Protein Tyrosine Phosphatase, Non-Receptor Type 11,
pubmed-meshheading:15133037-Protein Tyrosine Phosphatases,
pubmed-meshheading:15133037-Proto-Oncogene Proteins,
pubmed-meshheading:15133037-Recombinant Fusion Proteins,
pubmed-meshheading:15133037-SH2 Domain-Containing Protein Tyrosine Phosphatases,
pubmed-meshheading:15133037-Signal Transduction,
pubmed-meshheading:15133037-Transcription Factors,
pubmed-meshheading:15133037-Vault Ribonucleoprotein Particles,
pubmed-meshheading:15133037-ets-Domain Protein Elk-1
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pubmed:year |
2004
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pubmed:articleTitle |
The major vault protein is a novel substrate for the tyrosine phosphatase SHP-2 and scaffold protein in epidermal growth factor signaling.
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pubmed:affiliation |
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520-8066, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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