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 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.
Sayeski
P P
PP
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Ali
M S
MS
Hawks
K
K
Frank
S J
SJ
Bernstein
K E
KE
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002384:Catalysis; D002478:Cells, Cultured; D053614:Janus Kinase 2; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000737:chemistry*; D011518:Proto-Oncogene Proteins; D019061:src-Family Kinases / Q000737:chemistry*
D011518:Proto-Oncogene Proteins; D000804:Angiotensin II; D011505:Protein-Tyrosine Kinases; D053614:Janus Kinase 2; D019061:src-Family Kinases