TY - JOUR
T1 - Signaling through the hematopoietic cytokine receptors
AU - Ihle, James N.
AU - Witthuhn, Bruce A.
AU - Quelle, Frederick W.
AU - Yamamoto, Koh
AU - Silvennoinen, Olli
PY - 1995
Y1 - 1995
N2 - 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.
AB - 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.
KW - Janus kinases
KW - Stats
KW - cytokine receptor superfamily
KW - hemaotopoietic growth factor receptors
KW - hematopoietic growth factors
KW - interleukins
KW - protein tyrosine phosphorylation
KW - signal transduction
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U2 - 10.1146/annurev.iy.13.040195.002101
DO - 10.1146/annurev.iy.13.040195.002101
M3 - Review article
C2 - 7612228
AN - SCOPUS:0028933799
SN - 0732-0582
VL - 13
SP - 369
EP - 398
JO - Annual Review of Immunology
JF - Annual Review of Immunology
ER -