Angiotensin II signal transduction in vascular smooth muscle: role of tyrosine kinases.
In this review, the role of tyrosine kinases in angiotensin II-mediated signal transduction pathways in vascular smooth muscle is discussed. Angiotensin II was isolated by virtue of its vasoconstrictor abilities and has long been thought to play a critical role in hypertension. However, recent studies indicate important roles for angiotensin II in inflammation, atherosclerosis, and congestive heart failure. The expanding role of angiotensin II indicates that multiple signal transduction pathways are likely to be activated in a tissue-specific manner. Exciting recent data show that angiotensin II directly stimulates tyrosine kinases, including pp60(c-src) kinase (c-Src), focal adhesion kinase (FAK), and Janus kinases (JAK2 and TYK2). Angiotensin II may activate receptor tyrosine kinases, such as Axl and platelet-derived growth factor, by as-yet-undefined autocrine mechanisms. Finally, unknown tyrosine kinases may mediate tyrosine phosphorylation of Shc, Raf, and phospholipase C-gamma after angiotensin II stimulation. These angiotensin II-regulated tyrosine kinases appear to be required for angiotensin II effects, such as vasoconstriction, proto-oncogene expression, and protein synthesis, on the basis of studies with tyrosine kinase inhibitors. Thus, understanding angiotensin II-stimulated signaling events, especially those related to tyrosine kinase activity, may form the basis for the development of new therapies for cardiovascular diseases.
Berk
B C
BC
University of Washington, Department of Medicine, Seattle 98195, USA. bcberk@u.washington.edu
Corson
M A
MA
D000804:Angiotensin II / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology; D002478:Cells, Cultured; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000254:growth & development; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D015398:Signal Transduction / Q000502:physiology*; D019061:src-Family Kinases / Q000502:physiology
D015815:Cell Adhesion Molecules; C000715470:MAS1 protein, human; D010982:Platelet-Derived Growth Factor; D000090063:Proto-Oncogene Mas; D000804:Angiotensin II; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D019061:src-Family Kinases