Induction of cell shape changes through activation of the interleukin-3 common beta chain receptor by the RON receptor-type tyrosine kinase

The RON receptor-type tyrosine kinase, a member of the hepatocyte growth fa ctor receptor family, is a receptor for macrophage-stimulating protein (MSP ), Recently, we observed that MSP induces morphological changes in interleu kin (IL)-3-dependent Ba/F3 cells ectopically expressing RON. We show here t hat stimulation of those cells with either MSP or IL-3 increases tyrosine p hosphorylation of proteins of 130, 110, 90, 62, and 58 kDa and induces simi lar morphological changes, accompanied by unique nuclear shape and redistri bution of F-actin, A tyrosine kinase inhibitor, genistein, blocked both the increase in tyrosine phosphorylation and morphological changes. Upon stimu lation with either MSP or IL-3, prominent tyrosine-phosphorylated pp90 was similarly co-immunoprecipitated with the common beta chain of IL-3 receptor (beta(c)). Unlike IL-3, stimulation with MSP increased tyrosine phosphoryl ation of beta(c) without activation of JAK2, resulting in morphological cha nges with modest cell growth. Confocal immunofluorescence analyses showed c olocalization of RON, beta(c), and tyrosine-phosphorylated proteins. In vit ro kinase assays revealed that autophosphorylated RON phosphorylated beta(c ), These results suggest that the signaling pathway for morphological chang es through beta(c) and its associated protein pp90 is distinct from the pat hway for cell growth in the IL-3 signal transduction system.