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Endothelin‐1 induces Serine 910 phosphorylation of focal adhesion kinase via PKCdelta‐and Src‐dependent signaling pathways
Author(s) -
Chu Miensheng,
Iyengar Rekha,
Koshman Yevgeniya,
Kim Taehoon,
Samarel Allen M
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.620.3
Subject(s) - phosphorylation , protein kinase c , tyrosine phosphorylation , focal adhesion , proto oncogene tyrosine protein kinase src , rottlerin , chemistry , microbiology and biotechnology , signal transduction , kinase , endothelin 1 , ptk2 , serine , paxillin , biology , biochemistry , mitogen activated protein kinase kinase , receptor
Tyrosine phosphorylation of focal adhesion kinase (FAK) is well‐studied in cardiomyocytes, but little is known about FAK phosphorylation at serine residues. Stimulation of cultured neonatal rat ventricular myocytes (NRVM) with endothelin‐1 (ET‐1, 1–100nM, 2–30min) induced time‐ and dose‐dependent FAK S910 phosphorylation. Direct activation of protein kinase C (PKC) isoenzymes with phorbol 12‐myristate 13‐acetate (PMA, 200nM) significantly increased FAK S910 phosphorylation, whereas the PKC inhibitors GF102903X (10μM) and rottlerin (20μM), but not Gö6983 (10μM) prevented ET‐1‐induced FAK S910 phosphorylation. To distinguish the roles of individual PKC isoenzymes, constitutively active (CA) and dominant‐negative (DN) PKCα, PKCδ and PKCε were introduced into NRVM by adenovirus‐mediated gene transfer. ET‐1 induced FAK S910 phosphorylation was prevented by overexpression of DN‐PKCδ but not DN‐PKCα or DN‐PKCε. In contrast, only CA‐PKCδ induced FAK S910 phosphorylation. Treatment with MEK1 inhibitors U0126 (10μM) or PD98059 (25μM) and the Src inhibitor PP2 (10–20μM) also inhibited ET‐1 induced FAK S910 phosphorylation. We conclude that ET‐1 stimulates FAK S910 phosphorylation in NRVM via PKCδ‐MEK1‐ERK1/2 and Src‐MEK1‐ERK1/2 pathways. Supported PO1 HL62426 and the Falk Medical Research Trust.