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Biomechanical and neurohumoral stimulation of neonatal rat ventricular myocytes induce focal adhesion kinase phosphorylation at S910
Author(s) -
Chu Miensheng,
Iyenar Rekha,
Samarel Allen M
Publication year - 2009
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.23.1_supplement.lb56
Subject(s) - phosphorylation , focal adhesion , paxillin , microbiology and biotechnology , tyrosine phosphorylation , chemistry , proto oncogene tyrosine protein kinase src , kinase , signal transduction , protein kinase c , ptk2 , stimulation , medicine , endocrinology , biology , mitogen activated protein kinase kinase
Biomechanical and neurohumoral stimulation of cardiomyocytes rapidly increase focal adhesion kinase (FAK) phosphorylation at tyrosine residues, but little is known about FAK phosphorylation at serine residues. Stimulation of cultured neonatal rat ventricular myocytes (NRVM) by 20% static stretch promoted a 4‐5 fold increase in FAK S910 phosphorylation, but not S722 phosphorylation, as revealed by Western blotting with phosphospecific antibodies. The neurohumoral agonists endothelin‐1, angiotensin II, and phenylephrine also stimulated FAK S910 phosphorylation. Direct activation of protein kinase C isoforms with phorbol 12‐myristate 13‐acetate (PMA) significantly increased FAK S910 phosphorylation, whereas the PKC inhibitor GF102903X, but not Gö6983 prevented ET‐1‐induced FAK S910 phosphorylation. These results suggest that both stimulation increase FAK S910 phosphorylation via novel, but not classical PKCs. Treatment with the MEK1 inhibitors U0126 or PD98059 also inhibited FAK S910 phosphorylation in response to stretch and ET‐1, whereas the Src inhibitor PP2 reduced FAK S910 phosphorylation induced by ET‐1, but not by stretch. Furthermore, inhibition of ILK by shRNA‐mediated knockdown prevented stretch‐induced FAK S910 phosphorylation. Thus, these data demonstrate that biomechanical and neurohumoral stimuli stimulate NRVM FAK S910 phosphorylation via different signaling pathways.