title: Possible involvement of calcineurin, protein kinase C, and Src-family kinases in angiotensin II-induced tyrosine phosphorylation of p130cas in rat cardiac muscle.
abstract: Anigiotensin II (AII) has been documented to induce cardiac hypertrophy and rapid tyrosine phosphorylation of multiple intracellular substrates including 120 kD and 70 kD protein in cardiac cells. We have found that the 120 kD protein is a Crk-associated Src substrate, p130(cas). Specific inhibition of Src-family tyrosine kinases attenuated the AII-induced p130(cas) tyrosine phosphorylation. Either chelation of intracellular Ca(2+) or inhibition of protein kinase C resulted in the decrease of the phosphorylation. Further, we have investigated the relationship between the AII-induced p130(cas) tyrosine phosphorylation and a Ca(2+) and calmodulin dependent protein phosphatase calcineurin which is known to be involved in the signaling pathway of cardiac hypertrophy. Pretreatment with an immunosuppressant cyclosporin A, a specific inhibitor of calcineurin, resulted in the decrease of the phosphorylation. These findings strongly suggest that the AII-induced p130(cas) tyrosine phosphorylation might be associated with the signaling pathways of Src-family tyrosine kinases, protein kinase C and calcineurin in rat cardiac muscle.
authors.affiliation: Department of Legal Medicine, Osaka Medical College, Takatsuki 569-8686, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nishio
authors.forename: H
authors.initials: H
authors.lastname: Tsuji
authors.forename: A
authors.initials: A
authors.lastname: Tamura
authors.forename: K
authors.initials: K
authors.lastname: Suzuki