Abstract
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.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
