Homodimerization of IL‐2 receptor β chain is necessary and sufficient to activate Jak2 and dowstream signaling pathways

FEBS Letters

Buteau, Hélène²  Chiarenza, Andrea²  Goffin, Vincent²  Pezet, Alain²  Kelly, P.A²  Nelson, Brad H¹  Ferrag, Fatima² 

[1] Fred Hutchinson Cancer Research Center, 1124 Columbia Street, Seattle, WA 98104, USA;INSERM Unité 344 - Endocrinologie Moléculaire, Faculté de Médecine Necker, 156 rue de Vaugirard, 75730 Paris cedex 15, France

关键词: Cytokine receptor;    Janus kinase;    Specificity;    Dimerization;    Signal transduction;    R;    receptor;    PRL;    prolactin;    EPO;    erythropoietin;    SCF;    stem cell factor;    IL;    interleukin;    Jak;    Janus kinase;    Stat;    signal transducer and activator of transcription;    RTK;    receptor tyrosine kinase;    LIF;    leukemia inhibitory factor;    OSM;    oncostatin M;    CNTF;    ciliary neurotrophic factor;   

DOI  :  10.1016/S0014-5793(97)01529-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Cytokine receptor signaling involves the Jak/Stat pathways. Heterotrimeric IL-2R (α, β, γ_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-2Rβ chain fused to the extracellular domain of either EPOR or Kit, a non-cytokine receptor, activate Jak2. This observation provides evidence that IL-2Rβ 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.

【 授权许可】

Unknown