TY - JOUR
T1 - Electroporation of pp60c-src antibodies inhibits the angiotensin II activation of phospholipase C-γ1 in rat aortic smooth muscle cells
AU - Marrero, Mario B.
AU - Schieffer, Bernhard
AU - Paxton, William G.
AU - Schieffer, Elisabeth
AU - Bernstein, Kenneth E.
PY - 1995/6/30
Y1 - 1995/6/30
N2 - Our previous study has shown that angiotensin II induces the rapid tyrosine phosphorylation and activation of phospholipase C-γ1 in cultured rat aortic smooth muscle (RASM) cells (Marrero, M. B., Paxton, W. G., Duff, J. L., Berk, B. C., and Bernstein, K. E. (1994) J. Biol. Chem. 269, 10935-10939). This signaling pathway is initiated by ligand binding to the AT1 receptor, a cell surface G protein-coupled receptor. Antibodies to pp60c-Src were introduced into RASM cells by electroporation. Angiotensin II-stimulated tyrosine phosphorylation of phospholipase C-γ1 was eliminated by the anti-pp60c-src antibodies but not by anti-mouse IgG or bovine serum albumin. Angiotensin II also induced the rapid tyrosine phosphorylation of pp120, a known pp60c-src kinase substrate, and this phosphorylation was also specifically inhibited by anti-pp60c-arc antibodies. Electroporation of RASM cells with anti-pp60c-src antibodies had no effect on platelet-derived growth factor-stimulated tyrosine phosphorylation of PLC-γ1. Anti-pp60c-src also reduced the angiotensin II-stimulated inositol 1,4,5-trisphosphate production by 78%, while it had no effect on the platelet-derived growth factor-stimulated inositol 1,4,5-trisphosphate production. These data provide the first evidence for a direct involvement of pp60c-src kinase in angiotensin II-mediated PLC-γ1 phosphorylation and activation. Furthermore, it also describes a pathway in which a seven-transmembrane receptor can stimulate an intracellular tyrosine kinase.
AB - Our previous study has shown that angiotensin II induces the rapid tyrosine phosphorylation and activation of phospholipase C-γ1 in cultured rat aortic smooth muscle (RASM) cells (Marrero, M. B., Paxton, W. G., Duff, J. L., Berk, B. C., and Bernstein, K. E. (1994) J. Biol. Chem. 269, 10935-10939). This signaling pathway is initiated by ligand binding to the AT1 receptor, a cell surface G protein-coupled receptor. Antibodies to pp60c-Src were introduced into RASM cells by electroporation. Angiotensin II-stimulated tyrosine phosphorylation of phospholipase C-γ1 was eliminated by the anti-pp60c-src antibodies but not by anti-mouse IgG or bovine serum albumin. Angiotensin II also induced the rapid tyrosine phosphorylation of pp120, a known pp60c-src kinase substrate, and this phosphorylation was also specifically inhibited by anti-pp60c-arc antibodies. Electroporation of RASM cells with anti-pp60c-src antibodies had no effect on platelet-derived growth factor-stimulated tyrosine phosphorylation of PLC-γ1. Anti-pp60c-src also reduced the angiotensin II-stimulated inositol 1,4,5-trisphosphate production by 78%, while it had no effect on the platelet-derived growth factor-stimulated inositol 1,4,5-trisphosphate production. These data provide the first evidence for a direct involvement of pp60c-src kinase in angiotensin II-mediated PLC-γ1 phosphorylation and activation. Furthermore, it also describes a pathway in which a seven-transmembrane receptor can stimulate an intracellular tyrosine kinase.
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U2 - 10.1074/jbc.270.26.15734
DO - 10.1074/jbc.270.26.15734
M3 - Article
C2 - 7541047
AN - SCOPUS:0028982835
SN - 0021-9258
VL - 270
SP - 15734
EP - 15738
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 26
ER -