Linked Life Data

11882594

Source:http://linkedlifedata.com/resource/pubmed/id/11882594

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2 Pt 2
pubmed:dateCreated
2002-3-7
pubmed:abstractText
We investigated whether upregulation of Src by Ang II leads to increased extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) and whether these processes are associated with altered activation of C-terminal Src kinase (Csk), a negative regulator of Src. Furthermore, the role of epidermal growth factor receptor (EGFR) transactivation by angiotensin II (Ang II) was determined. Ang II-mediated c-Src phosphorylation was significantly greater (approximately 4-fold, P<0.01) in SHR than in Wistar-Kyoto rats (WKY). Ang II increased Csk phosphorylation 2-to 3-fold in WKY but not in SHR. Treatment of the cells with AG1478, a selective EGFR tyrosine kinase inhibitor, decreased Ang II-mediated c-Src phosphorylation, particularly in SHR. Phosphorylation of cortactin and Pyk2/focal adhesion kinase, Src-specific substrates, was increased by Ang II >3-fold, with significantly greater responses in SHR than in WKY (P<0.05). Ang II-induced ERK1/2 activation was significantly augmented (P<0.05) and sustained in VSMCs from SHR. PP2, a selective Src inhibitor, attenuated these effects and normalized the responses in SHR. Irbesartan, a selective Ang II type 1 receptor blocker, but not PD123319, a selective Ang II type 2 receptor blocker, inhibited Ang II actions. Our results demonstrate that c-Src phosphorylation and Src-dependent ERK1/2 signaling by Ang II are increased in VSMCs from SHR. These processes are associated with blunted Ang II-induced phosphorylation of Csk. EGFR transactivation contributes to Ang II-mediated Src-dependent ERK1/2 signaling. In conclusion, altered regulation of Ang II type 1 receptor-activated c-Src by Csk may be an important upstream modulator of abnormal ERK1/2 signaling in VSMCs from SHR.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1524-4563
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
479-85
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:11882594-Angiotensin II, pubmed-meshheading:11882594-Animals, pubmed-meshheading:11882594-Cells, Cultured, pubmed-meshheading:11882594-Enzyme Activation, pubmed-meshheading:11882594-Hypertension, pubmed-meshheading:11882594-Male, pubmed-meshheading:11882594-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:11882594-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:11882594-Mitogen-Activated Protein Kinases, pubmed-meshheading:11882594-Muscle, Smooth, Vascular, pubmed-meshheading:11882594-Phosphorylation, pubmed-meshheading:11882594-Protein-Tyrosine Kinases, pubmed-meshheading:11882594-Proto-Oncogene Proteins pp60(c-src), pubmed-meshheading:11882594-Rats, pubmed-meshheading:11882594-Rats, Inbred SHR, pubmed-meshheading:11882594-Rats, Inbred WKY, pubmed-meshheading:11882594-Receptor, Epidermal Growth Factor, pubmed-meshheading:11882594-Transcriptional Activation, pubmed-meshheading:11882594-src-Family Kinases
pubmed:year
2002
pubmed:articleTitle
Increased angiotensin II-mediated Src signaling via epidermal growth factor receptor transactivation is associated with decreased C-terminal Src kinase activity in vascular smooth muscle cells from spontaneously hypertensive rats.
pubmed:affiliation
Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, Montreal, Canada. touyzr@ircm.qc.ca
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't