Angiotensin II transduces its signal to focal adhesions via angiotensin II type 1 receptors in vascular smooth muscle cells.
In cultured vascular smooth muscle cells (VSMCs), angiotensin II (Ang II) stimulated tyrosine phosphorylation of several proteins including a cluster of 70-80-kDa proteins as assessed by anti-phosphotyrosine immunoblotting. These 70-80-kDa proteins were identified as a focal adhesion-associated protein, paxillin, by anti-paxillin immunoprecipitation. Ang II-stimulated tyrosine phosphorylation of paxillin was detectable within 1 min and maximal at around 10 min and was concentration dependent (half-maximal effect at around 1 nM). Ang II also stimulated tyrosine phosphorylation of focal adhesion kinase in a time- and concentration-dependent manner. The Ang II type 1 (AT1) receptor antagonist, CV-11974, but not the Ang II type 2 receptor antagonist, PD123319, inhibited these reactions. These results indicate that Ang II transduces its signal to focal adhesions via AT1 receptors in cultured VSMCs.
Okuda
M
M
Department of Internal Medicine (1st Division), Kobe University School of Medicine, Japan.
Kawahara
Y
Y
Nakayama
I
I
Hoshijima
M
M
Yokoyama
M
M
D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D007093:Imidazoles / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011945:Receptors, Angiotensin / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D007093:Imidazoles; D051419:Paxillin; D010750:Phosphoproteins; C496063:Pxn protein, rat; D011725:Pyridines; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496052:Ptk2 protein, rat; C081643:candesartan