Transactivation: a novel signaling pathway from angiotensin II to tyrosine kinase receptors

Angiotensin II (Ang II), an octapeptide pressor hormone, activates cellular events that may contribute to the pathogenesis of cardiovascular disease. The physiological actions of Ang II are mediated via the Ang II type 1 receptor (AT1R) and type 2 receptor (AT2R), which are G protein-coupled receptors (GPCR). GPCR share a common basic structure of seven transmembrane helices connected by alternating cytoplasmic and extracellular loops. GPCR lack intrinsic kinase activity possessed by receptor tyrosine kinases (RTK) such as platelet-derived growth factor receptor (PDGFR) or epidermal growth factor receptor (EGFR). Nonetheless, the signal transduction events activated by the AT1R mimic those of RTKs. Recently, cross-talk between GPCR and RTK has been observed. There is accumulating evidence that GPCR take advantage of signaling pathways downstream of RTK to exert its effect on the cells. In this context, RTK may be considered as one of signaling molecules downstream of GPCR.