MULTIPLE TYROSINE RESIDUES IN THE INTRACELLULAR DOMAIN OF THE COMMON BETA-SUBUNIT OF THE INTERLEUKIN-5 RECEPTOR ARE INVOLVED IN ACTIVATION OF STAT5

In contrast to the general model of cytokine-induced JAK/STAT signalin g, tyrosine phosphorylation of the IL-5R beta chain seems to be dispen sable for STAT activation in cells overexpressing exogenous STAT prote ins. In this study we expressed IL-5 receptor mutants in 293 cells and studied IL-5-induced endogenous STAT-dependent transcription. Our res ults indicate that: (a) tyrosine phosphorylation of the IL-SR beta cha in is required for endogenous STAT5 activation, (b) multiple tyrosine residues are phosphorylated upon IL-5 stimulation, including Tyr(577), Tyr(612), Tyr(695), and Tyr(750), and (c) Tyr(612), Tyr(695), and Tyr (750), all capable of inducing activation of STAT5, demonstrating a hi gh level of functional redundancy within the IL-5R beta chain. (C) 199 7 Federation of European Biochemical Societies.