The angiotensin II AT₁ receptor is tyrosine and serine phosphorylated and can serve as a substrate for the src family of tyrosine kinases

Angiotensin II AT₁ receptor signal transduction has recently been shown to function through the phospholipase C isozyme, PLC-γ. Since PLC-γ is known to interact with phosphotyrosine containing proteins through SH₂ domains, we examined the phosphorylation state of the AT₁ receptor. Immunoprecipitation of the [³²P] labeled AT₁ receptor from rat aortic smooth muscle cells followed by alkali hydrolysis demonstrated the presence of tyrosine phosphorylation. Phosphoamino acid analysis of the excised bands demonstrated the presence of phosphoserine and phosphotyrosine residues. A fusion protein comprising the intracellular tail of the AT₁ receptor was used to screen for candidate kinases, and the src kinase family displayed high activity. In summary, this study shows that the AT₁ receptor is serine and tyrosine phosphorylated in vivo and suggests that a soluble kinase related to the src family may be responsible for the tyrosine phosphorylation.