HOMODIMERIZATION OF IL-2 RECEPTOR-BETA CHAIN IS NECESSARY AND SUFFICIENT TO ACTIVATE JAK2 AND DOWSTREAM SIGNALING PATHWAYS

Cytokine receptor signaling involves the Jak/Stat pathways. Heterotrim eric IL-2R (alpha, beta, gamma(c), chains) activates Jak1 and Jak3, wh ereas homodimeric PRLR activates Jak2., The requirements directing suc h specificity of Jak activation are unknown. We show that chimeric rec eptors containing the intracellular domain of IL-2R beta chain fused t o the extracellular domain of either EPOR or Kit, a non-cytokine recep tor, activate Jak2., This observation, provides evidence that IL-2R be ta intrinsically possesses the ability to activate Jak2, but that this property is only displayed in homodimerized complexes., Our data sugg est a role for the stoichiometry of cytokine receptors in selective ac tivation of Janus kinases, (C) 1998 Federation of European Biochemical Societies.