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Signaling Through the Hematopoietic Cytokine Receptors

Signaling Through the Hematopoietic Cytokine Receptors Hematopoiesis is regulated through the interaction of a variety of growth factors with specific receptors of the cytokine receptor superfamily. Although lacking catalytic domains, all the receptors couple ligand binding to the rapid induction of protein tyrosine phosphorylation. This is mediated through a novel family of protein tyrosine kinases termed the Janus kinases (Jaks) which associate with the receptors and are activated following ligand binding. Depending upon the cytokine/receptor system, one or more of the four known Jaks (Jak l , Jak2, Jak3, lYk2) is/are involved. The activated Jaks phosphorylate both themselves and the receptor subunits, creating docking sites for SH2-containing proteins including SHC, which couples receptor engagement to activation of the ras pathway, and HCP, a protein tyrosine phosphatase which negatively affects the response. In addition, the Iaks phosphorylate one or more of a family of signal transducers and activators of transcription (Stats). Phosphorylation of Stats induces their nuclear translocation and DNA-binding activity. Activation of Stats is independent of activation of the ras pathway and represents a novel signaling pathway correlated with mitogenesis. INTRODUCTION The proliferation and differentiation of the cells that give rise to all the myeloid and lymphoid lineages are controlled by one or more http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annual Review of Immunology Annual Reviews

Signaling Through the Hematopoietic Cytokine Receptors

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Publisher
Annual Reviews
Copyright
Copyright 1995 Annual Reviews. All rights reserved
Subject
Review Articles
ISSN
0732-0582
eISSN
1545-3278
DOI
10.1146/annurev.iy.13.040195.002101
pmid
7612228
Publisher site
See Article on Publisher Site

Abstract

Hematopoiesis is regulated through the interaction of a variety of growth factors with specific receptors of the cytokine receptor superfamily. Although lacking catalytic domains, all the receptors couple ligand binding to the rapid induction of protein tyrosine phosphorylation. This is mediated through a novel family of protein tyrosine kinases termed the Janus kinases (Jaks) which associate with the receptors and are activated following ligand binding. Depending upon the cytokine/receptor system, one or more of the four known Jaks (Jak l , Jak2, Jak3, lYk2) is/are involved. The activated Jaks phosphorylate both themselves and the receptor subunits, creating docking sites for SH2-containing proteins including SHC, which couples receptor engagement to activation of the ras pathway, and HCP, a protein tyrosine phosphatase which negatively affects the response. In addition, the Iaks phosphorylate one or more of a family of signal transducers and activators of transcription (Stats). Phosphorylation of Stats induces their nuclear translocation and DNA-binding activity. Activation of Stats is independent of activation of the ras pathway and represents a novel signaling pathway correlated with mitogenesis. INTRODUCTION The proliferation and differentiation of the cells that give rise to all the myeloid and lymphoid lineages are controlled by one or more

Journal

Annual Review of ImmunologyAnnual Reviews

Published: Apr 1, 1995

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