Regulation of calcium-sensitive tyrosine kinase Pyk2 by angiotensin II in endothelial cells - Roles of Yes tyrosine kinase and tyrosine phosphatase SHP-2
H. Tang et al., Regulation of calcium-sensitive tyrosine kinase Pyk2 by angiotensin II in endothelial cells - Roles of Yes tyrosine kinase and tyrosine phosphatase SHP-2, J BIOL CHEM, 275(12), 2000, pp. 8389-8396
Calcium-sensitive tyrosine kinase Pyk2 has been implicated in the regulatio
n of ion channels, cellular adhesion, and mitogenic and hypertrophic reacti
ons. In this study, we have investigated the regulation of Pyk2 by angioten
sin II (Ang II) in pulmonary vein endothelial cells. We found that the Ang
II-induced tyrosine phosphorylation of Pyk2, which requires the activity of
Src family kinase, was specifically regulated by the Src family kinase mem
ber, Yes kinase, Moreover, we identified for the first time the constitutiv
e association of Pyk2 with an Src homology 2 (SH2) domain-containing tyrosi
ne phosphatase SHP-2. SHP-2 interacts with Pyk2 through a region other than
its SH2 domains. Pyk2 can be dephosphorylated in vitro in SHP-2 immunoprec
ipitates and in intact cells expressing an NH, terminus-truncated form of S
HP-2, which lacks the two SH2 domains but has an enhanced phosphatase activ
ity. Ang II activates the endogenous SHP-2, Finally, the SHP-2-mediated dep
hosphorylation of Pyk2 correlates with the negative effect of SHP-2 on the
Ang II-induced activation of extracellular signal-regulated kinase and c-Ju
n NH2-terminal kinase. Thus, the balance of Pyk2 tyrosine phosphorylation i
n response to Ang II is controlled by Yes kinase and by a tyrosine phosphat
ase SHP-2 in endothelial cells.