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  • Ang II binding to AT1-R triggers the activation of Ca2+ signaling and PKC. The signal is then transmitted to Pyk2 and to the small G protein Rac1 but not Cdc42. In turn, Rac1 activates a small G protein-activated kinase whose identity is still controversial, but which has been suggested to be PAK1. Finally, the JNK cascade, including MEKK1, SEK1, and JNK, is activated, causing induction of the c-Jun gene via binding of ATF2 and c-Jun heterodimer to the junTRE2 site. Ang II is closely involved in 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. The collagenase gene, containing 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. (This definition may be outdated - see the DesignNote.)
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