© 1999 American Heart Association, Inc.
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The Angiotensin II–Dependent Association of Jak2 and c-Src Requires the N-Terminus of Jak2 and the SH2 Domain of c-Src
From the Department of Pathology and Laboratory Medicine (P.P.S., M.S.A., K.H., K.E.B.), Emory University School of Medicine, Atlanta, Ga; Department of Medicine (S.J.F.), Division of Endocrinology and Metabolism, University of Alabama at Birmingham, Birmingham, Ala.
Correspondence to Kenneth E. Bernstein, Department of Pathology and Laboratory Medicine, 1639 Pierce Dr, 7107 WMB, Emory University School of Medicine, Atlanta, GA 30322. E-mail kbernst{at}emory.edu
Abstract—The binding of angiotensin II (Ang II) to AT1 is known to increase the kinase activity of several nonreceptor tyrosine kinases including Jak2 and c-Src. In the present study, we demonstrate that treatment of vascular smooth muscle cells with Ang II results in a rapid and transient association of Jak2 and c-Src. This association is dependent on a catalytically active Jak2 kinase, because it is blocked both by pharmacological means and by the inability 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 unphosphorylated Jak2 protein, indicating that the SH2 domain of c-Src mediates this association. In vivo studies indicated that c-Src binds the N-terminus of Jak2 as expression of a Jak2 molecule lacking the initial 240 amino acids, including 16 tyrosines, and was unable to bind c-Src. Lastly, using transiently transfected COS-7 cells, we found that Ang II treatment induced an association between c-Src and wild-type Jak2 but not between c-Src and the Jak2 molecule that lacks the initial 240 amino acids. Thus, our data suggest that in addition to increasing the kinase activities Jak2 and c-Src, treatment of cells with Ang II results in the physical association of Jak2 and c-Src; an association that is mediated by the SH2 domain of c-Src and the N-terminus of Jak2.
Key Words: angiotensin II • Jak2 • c-Src • tyrosine kinase • vascular smooth muscle cell
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