Preassociation of nonactivated STAT3 molecules demonstrated in living cells using bioluminescence resonance energy transfer: a new model of STAT activation?

Journal of Leukocyte Biology

Karen M. Kroeger¹  Hans-Dieter Volk²  Martina Schröder²  Gerald Grütz²  Karin A. Eidne¹ 

[1] The Center for Medical Research, University of Western Australia, The Western Australian Institute for Medical Research, Sir Charles Gairdner Hospital, Nedlands, Perth, Australia The Center for Medical Research, University of Western Australia, The Western Australian Institute for Medical Research, Sir Charles Gairdner Hospital, Nedlands, Perth, Australia The Center for Medical Research, University of Western Australia, The Western Australian Institute for Medical Research, Sir Charles Gairdner Hospital, Nedlands, Perth, Australia;Institute of Medical Immunology, Humboldt-University (Charite) Berlin, Germany; and Institute of Medical Immunology, Humboldt-University (Charite) Berlin, Germany; and Institute of Medical Immunology, Humboldt-University (Charite) Berlin, Germany; and

关键词: cytokine;    signal transduction;    dimerization signal transducer and activator of transcription (STAT);    energy transfer;    BRET;   

DOI  :  10.1189/jlb.1003496

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Signal transducers and activators of transcription (STATs) are crucial molecules in cytokine signaling. In the conventional model of STAT activation, STAT molecules are recruited from a latent pool of cytoplasmic monomers to the activated cytokine receptor. After binding to the receptor, they get tyrosine-phosphorylated, dissociate from the receptor, and translocate to the nucleus as activation-induced dimers. Recently, several publications questioned this model of STAT activation and showed the existence of preassociated STAT molecules before activation. We were able to demonstrate the existence of these preassociated STAT3 molecules in living mammalian cells using bioluminescence resonance energy transfer. Our results support the new hypothesis that STAT molecules exist in the cytoplasm as dimers or multimers and point to an activation-induced change in STAT3 conformation. Therefore, we propose a new model of STAT activation and discuss a hypothetical structure of “cytoplasmic” STAT dimers as opposed to the known “activation-induced” dimer.

【 授权许可】

Unknown