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Requirement of c‐Src in Angiotensin II and Endothelin 1‐induced Activation of MAPKinases in Vascular Smooth Muscle Cells (VSMC)
Author(s) -
Vardatsikos George,
Kapakos Georgia,
Srivastava Ashok K.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.868.1
Subject(s) - angiotensin ii , vascular smooth muscle , proto oncogene tyrosine protein kinase src , signal transduction , medicine , kinase , phosphorylation , protein kinase b , endocrinology , endothelin 1 , chemistry , tyrosine kinase , tyrosine phosphorylation , mapk/erk pathway , microbiology and biotechnology , biology , receptor , smooth muscle
Endothelin‐1 (ET‐1) and Angiotensin II (Ang II), two important vasoactive peptides, have been implicated in the pathogenesis of vascular abnormalities such as hypertension and atherosclerosis, through the activation of growth promoting signal transduction pathways, which include mitogen‐activated protein kinases (MAPKs) and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (PKB). We have previously shown that c‐Src, a non‐receptor protein tyrosine kinase (NR‐PTK), is an upstream regulator of ET‐1 and Ang II‐induced activation of PKB in VSMC. However, the role of c‐Src in ET‐1‐induced MAPK signaling remains controversial in VSMC. Therefore, in the present studies, we have investigated the involvement of c‐Src in this process. Treatment of VSMC with ET‐1 and Ang II induced phosphorylation of ERK1/2, JNK and p38MAPK in A10 VSMC and in aortic VSMC isolated from 12 week old Wistar Kyoto rats (WK‐VSMC). PP2, an inhibitor of the Src family of NR‐PTK, decreased phosphorylation of ERK1/2, JNK and p38MAPK induced by both ET‐1 and Ang II in a dose‐dependent fashion. Furthermore, knockdown of c‐Src by siRNA also exhibited a similar response, and inhibited ET‐1 and Ang II‐induced ERK1/2, JNK and p38MAPK phosphorylation. In summary, these data suggest that both ET‐1 and Ang II signal the activation of MAPKs through a c‐Src dependent mechanism in VSMC. (Supported by grants from Canadian Institutes of Health Research).