Insulin selectively activates STAT5b, but not STAT5a, via a JAK2-independent signalling pathway in Kym-1 rhabdomyosarcoma cells

The STAT multigene family of transcriptional regulators conveys signals fro m several cytokines and growth factors upon phosphorylation by janus kinase s (JAK), Activation of STAT5 is typically mediated by JAK2, but more recent data indicate a direct activation by the insulin receptor kinase, STAT5 ex ists in two closely homologous isoforms, STAT5a and b, We here describe the selective tyrosine phosphorylation of STAT5b in Kym-1 cells in response to insulin. Blocking insulin signalling by HNMPA-(AM)(3), an insulin receptor kinase inhibitor, resulted in the loss of insulin-induced STAT5b tyrosine phosphorylation, whereas the inhibition of JAK2 by the JAK selective inhibi tor tyrphostin AG490 had no effect, By contrast, in the same cells, IFN gam ma-induced STAT5b activation was JAK2-dependent, indicating that this signa l pathway is functional in Kym-1 cells. We conclude from this rhabdomyosarc oma model that STAT5b, but not STAT5a is a direct target of the insulin rec eptor kinase. (C) 1999 Federation of European Biochemical Societies.