Multiple tyrosine residues in the intracellular domain of the common β subunit of the interleukin 5 receptor are involved in activation of STAT5

In contrast to the general model of cytokine-induced JAK/STAT signaling, tyrosine phosphorylation of the IL-5R β chain seems to be dispensable for STAT activation in cells overexpressing exogenous STAT proteins. In this study we expressed IL-5 receptor mutants in 293 cells and studied IL-5-induced endogenous STAT-dependent transcription. Our results indicate that: (a) tyrosine phosphorylation of the IL-5R β chain is required for endogenous STAT5 activation, (b) multiple tyrosine residues are phosphorylated upon IL-5 stimulation, including Tyr⁵⁷⁷, Tyr⁶¹², Tyr⁶⁹⁵ and Tyr⁷⁵⁰, and (c) Tyr⁶¹², Tyr⁶⁹⁵, and Tyr⁷⁵⁰ are all capable of inducing activation of STAT5, demonstrating a high level of functional redundancy within the IL-5R β chain.