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Homodimerization of IL-2 receptor beta chain is necessary and sufficient to activate Jak2 and downstream signaling
F Ferrag1, A Pezet, A Chiarenza
1INSERM Unité 344 - Endocrinologie Moléculaire, Faculté de Médecine Necker, Paris, France.
Abstract:
Cytokine receptor signaling involves the Jak/Stat pathways. Heterotrimeric IL-2R (alpha, beta, gamma[c] chains) activates Jak1 and Jak3, whereas homodimeric PRLR activates Jak2. The requirements directing such specificity of Jak activation are unknown. We show that chimeric receptors containing the intracellular domain of IL-2Rbeta chain fused to the extracellular domain of either EPOR or Kit, a non-cytokine receptor, activate Jak2. This observation provides evidence that IL-2Rbeta intrinsically possesses the ability to activate Jak2, but that this property is only displayed in homodimerized complexes. Our data suggest a role for the stoichiometry of cytokine receptors in selective activation of Janus kinases.