Signaling through the hematopoietic cytokine receptors

James N. Ihle, Bruce A. Witthuhn, Frederick W. Quelle, Koh Yamamoto, Olli Silvennoinen

Research output: Contribution to journalReview articlepeer-review

530 Scopus citations

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 (Jak1, Jak2, Jak3, Tyk2) 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.

Original languageEnglish (US)
Pages (from-to)369-398
Number of pages30
JournalAnnual Review of Immunology
Volume13
DOIs
StatePublished - 1995

Keywords

  • Janus kinases
  • Stats
  • cytokine receptor superfamily
  • hemaotopoietic growth factor receptors
  • hematopoietic growth factors
  • interleukins
  • protein tyrosine phosphorylation
  • signal transduction

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