Glycogen synthase kinase 3 beta is tyrosine phosphorylated by PYK2

Glycogen synthase kinase 3 beta (GSK3 beta) is a Ser/Thr kinase that is inv olved in numerous cellular activities. GSK3 beta is activated by tyrosine p hosphorylation. However, very little is known about the tyrosine kinases th at are responsible for phosphorylating GSK3 beta. In this report, we invest igated the ability of the calcium-dependent tyrosine kinase, proline-rich t yrosine kinase 2 (PYK2) to tyrosine phosphorylate GSK3 beta. In transfected CHO cells, it was demonstrated that PYK2 tyrosine phosphorylates GSK3 beta in situ. The two kinases also coimmunoprecipitated. Furthermore, GSK3 beta was tyrosine phosphorylated in vitro by an active, wild type PYK2, but not by the inactive, kinase dead form of PYK2. Therefore, this study is the fi rst to demonstrate that GSK3 beta is a substrate of PYK2 both in vitro and in situ. (C) 2001 Academic Press.