PMID: 9418183Jan 7, 1998Paper

Advances in the understanding of cytokine signal transduction: the role of Jaks and STATs in immunoregulation and the pathogenesis of immunodeficiency

Journal of Clinical Immunology
John J O'SheaF Candotti

Abstract

Cytokines are of great importance in the growth and differentiation of hematopoietic and other cells. Moreover, they are also crucial in immunoregulation and in host defense. Although our understanding of the molecular basis of cytokine action is far from complete, recent advances have substantially improved our knowledge of cytokine-dependent signal transduction. The delineation of the structure of cytokine receptors and the signaling pathways they utilize has provided clues as to how the strikingly specific effects of cytokines are achieved. Additionally, the basis of some of the pleiotropic and redundant effects of cytokines has also become clear. The discovery of the Janus family of protein tyrosine kinases (Jaks) and the STATs (signal transducers and activators of transcription) has also provided key insights into the mechanism by which intracellular signals are transduced. The following paradigm has emerged: cytokines induce dimerization of receptor subunits that are constitutively associated with Jaks. This activates the Jaks, which then phosphorylate the receptors. The phosphorylated receptors are bound by SH2-containing proteins, one class of which is the STATs. Activated STATs, then, translocate to the nucleus to effe...Continue Reading

Citations

Feb 9, 2012·Molecular Biology Reports·Jing HuangShu-Hong Zhao
May 25, 2016·Clinical Reviews in Allergy & Immunology·Aleš GoropevšekTadej Avčin
Feb 10, 2017·Annual Review of Immunology·Thomas A Waldmann, Jing Chen
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Sep 15, 2001·American Journal of Physiology. Lung Cellular and Molecular Physiology·N J CartelM Post
Jun 25, 2015·Frontiers in Immunology·Debendra PattanaikArnold E Postlethwaite
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