Linked Life Data

11851354

Source:http://linkedlifedata.com/resource/pubmed/id/11851354

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-2-19
pubmed:abstractText
G protein-coupled receptor (GPCR)-evoked signal transduction pathways leading to the activation of extracellular signal-regulated kinases (ERK) are quite different among cell types. In cardiomyocytes, much attention has been focused on the activation of protein kinase C (PKC) or mobilization of intracellular Ca(2+) ([Ca(2+)](i)), however, the contributions of tyrosine kinases are controversial. In the present study, we characterized the signaling pathways involving tyrosine kinases, Pyk2 and epidermal growth factor receptor (EGFR), and their contribution to ERK activation in cultured cardiomyocytes. We initially investigated the potential involvement of [Ca(2+)](i) and PKC on the activation of these kinases in endothelin-stimulated cardiomyocytes. Interestingly, activation of Pyk2 was abrogated by chelating [Ca(2+)](i) or by downregulation of PKC, whereas transactivation of EGFR was solely dependent on PKC. By using a compound that selectively interferes with EGFR (AG1478), c-Src (PP1), or disrupts actin cytoskeleton (cytochalasin D), we demonstrated that cytochalasin D completely inhibited the activation of Pyk2, but not that of EGFR, whereas AG1478 did not inhibit the activation of Pyk2, indicating that transactivation of EGFR and signaling pathways involving Pyk2 were distinct pathways. Furthermore, activation of ERK and Shc, and c- fos gene expression were significantly inhibited by AG1478 but not by cytochalasin D or PP1. Overexpression of deletion mutant of EGFR attenuated the activation of ERK. These facts demonstrated the existence of two distinct tyrosine kinase pathways requiring Pyk2 or EGFR downstream from GPCR in cardiomyocytes. EGFR was Ca(2+)-independently activated and predominantly contributed to Shc/ERK/c- fos activation, while Pyk2 or c-Src contributed less to it.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-2828
pubmed:author
pubmed:copyrightInfo
Copyright 2002 Academic Press.
pubmed:issnType
Print
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
139-50
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Role of EGF Receptor and Pyk2 in endothelin-1-induced ERK activation in rat cardiomyocytes.
pubmed:affiliation
Cardiopulmonary Division, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't