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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2003-12-22
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pubmed:abstractText |
The heptahelical AT(1) G-protein-coupled receptor lacks inherent tyrosine kinase activity. Angiotensin II binding to AT(1) nevertheless activates several tyrosine kinases and stimulates both tyrosine phosphorylation and phosphatase activity of the SHP-2 tyrosine phosphatase in vascular smooth muscle cells. Since a balance between tyrosine kinase and tyrosine phosphatase activities is essential in angiotensin II signaling, we investigated the role of SHP-2 in modulating tyrosine kinase signaling pathways by stably transfecting vascular smooth muscle cells with expression vectors encoding wild-type SHP-2 protein or a catalytically inactive SHP-2 mutant. Our data indicate that SHP-2 is an efficient negative regulator of angiotensin II signaling. SHP-2 inhibited c-Src catalytic activity by dephosphorylating a positive regulatory tyrosine 418 within the Src kinase domain. Importantly, SHP-2 expression also abrogated angiotensin II-induced activation of ERK, whereas expression of catalytically inactive SHP-2 caused sustained ERK activation. Thus, SHP-2 likely regulates angiotensin II-induced MAP kinase signaling by inactivating c-Src. These SHP-2 effects were specific for a subset of angiotensin II signaling pathways, since SHP-2 overexpression failed to influence Jak2 tyrosine phosphorylation or Fyn catalytic activity. These data show SHP-2 represents a critical negative regulator of angiotensin II signaling, and further demonstrate a new function for this phosphatase in vascular smooth muscle 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/CSK tyrosine-protein kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, Serum-Free,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Jak2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ptpn11 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Angiotensin, Type 1
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0898-6568
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
16
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
301-11
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:14687660-Animals,
pubmed-meshheading:14687660-Aorta,
pubmed-meshheading:14687660-Cells, Cultured,
pubmed-meshheading:14687660-Culture Media, Serum-Free,
pubmed-meshheading:14687660-Down-Regulation,
pubmed-meshheading:14687660-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:14687660-Janus Kinase 2,
pubmed-meshheading:14687660-Muscle, Smooth, Vascular,
pubmed-meshheading:14687660-Phosphorylation,
pubmed-meshheading:14687660-Protein Tyrosine Phosphatase, Non-Receptor Type 1,
pubmed-meshheading:14687660-Protein Tyrosine Phosphatase, Non-Receptor Type 11,
pubmed-meshheading:14687660-Protein Tyrosine Phosphatases,
pubmed-meshheading:14687660-Protein-Tyrosine Kinases,
pubmed-meshheading:14687660-Proto-Oncogene Proteins,
pubmed-meshheading:14687660-Rats,
pubmed-meshheading:14687660-Receptor, Angiotensin, Type 1,
pubmed-meshheading:14687660-Signal Transduction
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pubmed:year |
2004
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pubmed:articleTitle |
Selective down-regulation of angiotensin II receptor type 1A signaling by protein tyrosine phosphatase SHP-2 in vascular smooth muscle cells.
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pubmed:affiliation |
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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