Angiotensin II mediated activation of JNK Pathway via Pyk2 dependent
Ang II binding to AT1-R triggers the activation of Ca2+ signaling and PKC. The signal is then transmitted to the Pyk2 and further to the small G protein Rac1 but not Cdc42, although the direct activation of Rac1 by Pyk2 is not proved in this study. In turn, Rac1 activates a small G protein-activated kinase whose identity is still controversial, but one of which has been suggested to be PAK1. Finally, the JNK cascade, including MEKK1, SEK1, and JNK, is activated, causing induction of c-Jun gene via binding of ATF2 and c-Jun heterodimer to the junTRE2 site. Ang II is closely involved in the cardiac remodeling by stimulating synthesis of extracellular matrix proteins. It was recently found that expression of fibronectin by Ang II is transcriptionally regulated by AP-1 complex in cardiac fibroblasts. Collagenase gene containg AP-1 sites is also regulated by AP-1 components including c-Jun. AP-1 activity is also enhanced in Ang II-induced cardiac hypertrophy. Expression of ANF is regulated by AP-1 components.
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REFERENCES: Satoshi Murasawa, et al. Angiotensin II Initiates Tyrosine Kinase Pyk2-dependent Signalings Leading to Activation of Rac1-mediated c-Jun NH2-terminal Kinase. Journal of Biological Chemistry, 2000, 275(35), 26856-26863.
