Titre
Advances in the understanding of cytokine signal transduction: the role of Jaks and STATs in immunoregulation and the pathogenesis of immunodeficiency
Type
synthèse (review)
Institution
Externe
Périodique
Auteur(s)
O'Shea, J. J.
Auteure/Auteur
Notarangelo, L. D.
Auteure/Auteur
Johnston, J. A.
Auteure/Auteur
Candotti, F.
Auteure/Auteur
Liens vers les personnes
ISSN
0271-9142
Statut éditorial
Publié
Date de publication
1997-11
Volume
17
Numéro
6
Première page
431
Dernière page/numéro d’article
47
Langue
anglais
Notes
O'Shea, J J
Notarangelo, L D
Johnston, J A
Candotti, F
eng
Review
Netherlands
J Clin Immunol. 1997 Nov;17(6):431-47.
Notarangelo, L D
Johnston, J A
Candotti, F
eng
Review
Netherlands
J Clin Immunol. 1997 Nov;17(6):431-47.
Résumé
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 effect gene transcription. Though the Jaks do not explain much in terms of specificity in signaling, the function of the STATs does. The discovery of patients with autosomal recessive severe combined immunodeficiency due to mutations of a particular Jak, Jak3, and the phenotype of knockout mice lacking Jak3 and various STATs demonstrate the specific and critical roles of these molecules in the development and function of the immune system.
PID Serval
serval:BIB_D8ECA633403E
PMID
Date de création
2017-11-01T09:29:28.919Z
Date de création dans IRIS
2025-05-20T23:28:57Z