Smooth muscle activation kinase cascades

ET-1 also stimulates anti-apoptotic signal cascades in fibroblasts, vascular smooth muscles and endothelial cells (via phosphatidylinositol-3-kinase and Akt/pro-tein kinase B). In prostate and ovarian cancer, upregulation of endothelin synthesis and ETA receptors has been associated with a progression of the disease. The inhibiton of ETA receptors results in a reduced tumour growth. In malignant melanoma, ETB receptors are associated with tumour progression. Endothelins can also stimulate apoptosis in stretch-activated vessels via the ETB receptor, which contrasts the above-mentioned effects. The molecular basis for these differential anti- and pro-apoptotic reactions mediated by endothelins remains elusive. 

Mori-Abe A, Tsutsumi S, Takahashi K, Toya M, Yoshida M, Du B, Kawagoe J, Naka-hara K, Takahashi T, Ohmichi M, Kurachi H (2003) Estrogen and raloxifene induce apoptosis by activating p38 mitogen-activated protein kinase cascade in synthetic vascular smooth muscle cells. J Endocrinol 178 417-426... 

Eguchi, S., Matsumoto, T., Motley, E. D., et al. 1996. Identification of an essential signaling cascade for mitogen-activated protein kinase activation by angiotensin II in cultured rat vascular smooth muscle cells. Possible requirement of Gq-mediated p21ras activation coupled to a Ca2+/calmodulin-sensitive tyrosine kinase. J Biol Chem 271 14169-14175. 

Kitazawa T, Kobayashi S, Horiuti K, Somlyo AV, Somlyo AP (1989) Receptor-coupled, permeabilized smooth muscle. Role of the phosphatidylinositol cascade, G-proteins, and modulation of the contractile response to Ca . J Biol Chem 264 5339-5242 Klemke RL, Cai S, Giannini AL, Gallagher PJ, de Lanerolle P, Cheresh DA (1997) Regulation of cell motility by mitogen-activated protein kinase. J Cell Biol 137 481-492... 

Abraham ST, Benscoter HA, Schworer CM, Singer HA (1997) A role for Ca /calmodulin-dependent protein kinase II in the mitogen-activated protein kinase signaling cascade of cultured rat aortic vascular smooth muscle cells. Circ Res 81 575-584... 

Figure 3 The cascade for vasodilation In mammals. Acetylcholine or bradykinin activates endothelial membrane receptors and activates the eNOS enzyme by enhancing the Intracellular calcium levels. The NO diffuses into the adjacent smooth muscle cells, where it stimulates the guanylate cyclase enzyme to produce cGMP. The latter activates protein kinase G, which stimulates outflux of K+ and Ca + from the cell. The drop in intracellular calcium triggers the relaxation of the muscle tissue. Alternatively, the guanylate cyclase In the smooth muscle cells may be activated by pharmaceutical NO donors in the bloodstream.

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