The angiotensin II-dependent association of Jak2 and c-Src requires the N-terminus of Jak2 and the SH2 domain of c-Src

The binding of angiotensin 11 (Ang II) to AT, is known to increase the kina se activity of several nonreceptor tyrosine kinases including Jak2 and c-Sr c. In the present study, we demonstrate that treatment of vascular smooth m uscle cells with Ang Il results in a rapid and transient association of Jak 2 and c-Src. This association is dependent on a catalytically active Jak2 k inase, because it is blocked both by pharmacological means and by the inabi lity of a catalytically inactive Jak2 to associate with c-Src. c-Src bound tyrosine phosphorylated Jak2 but was unable to bind an equal, amount of unp hosphorylated Jak2 protein, indicating that the SH2 domain of c-Src mediate s this association. In vivo studies indicated that c-Src binds the N-termin us of Jak2 as expression of a Jak2 molecule lacking the initial 240 amino a cids, including 16 tyrosines, and was unable to bind c-Src. Lastly, using t ransiently transfected COS-7 cells, we found that Ang II treatment induced an association between c-Src and wild-type Jak2 but nor between c-Src and t he Jak2 molecule that lacks the initial 240 amino acids. Thus, our data sug gest that in addition to increasing the kinase activities Jak2 and c-Src, t reatment of cells with Ang II results in the physical association of Jak2 a nd c-Src; an association that is mediated by the SH2 domain of c-Src and th e N-terminus of Jak2.