Tyrosine phosphorylation and association of p130Cas and c-Crk II by ANG II in vascular smooth muscle cells.
In cultured vascular smooth muscle cells (VSMC), angiotensin II (ANG II) stimulated tyrosine phosphorylation of multiple proteins including a 130-kDa protein. This 130-kDa protein was identified as a Crk-associated substrate, p130Cas. ANG II-stimulated tyrosine phosphorylation of p130Cas was rapid, concentration dependent, and inhibited by the AT1-receptor antagonist CV-11974. Neither downregulation of protein kinase C by long exposure of cells to phorbol 12,13-dibutyrate nor blockade of Ca2+ mobilization by 1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester had an effect on ANG II-stimulated tyrosine phosphorylation of p130Cas. Stimulation with ANG II enhanced the specific association of p130Cas with c-Crk II. The time course of the association of p130Cas and c-Crk II was similar to that of tyrosine phosphorylation of p130Cas. c-Crk II was also tyrosine phosphorylated in response to ANG II. These results indicate that ANG II induces tyrosine phosphorylation of p130Cas and c-Crk II and their specific association, suggesting a potential role of the p130Cas-c-Crk II complex in ANG II signal transduction in VSMC.
Takahashi
T
T
Department of Internal Medicine, Kobe University School of Medicine, Japan.
Kawahara
Y
Y
Taniguchi
T
T
Yokoyama
M
M
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D050719:Crk-Associated Substrate Protein; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000502:physiology; D011494:Protein Kinases / Q000378:metabolism*; D011506:Proteins; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D051381:Rats; D011945:Receptors, Angiotensin / Q000502:physiology; D050717:Retinoblastoma-Like Protein p130; D014443:Tyrosine / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
C493843:Bcar1 protein, rat; C493872:Crk protein, rat; D050719:Crk-Associated Substrate Protein; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D011945:Receptors, Angiotensin; D050717:Retinoblastoma-Like Protein p130; D010566:Virulence Factors, Bordetella; D000804:Angiotensin II; D014443:Tyrosine; D011494:Protein Kinases; D011493:Protein Kinase C; D002118:Calcium