Roles of tyrosine phosphorylalion and JAK2 in hGM-CSF signal transduction S

Watanabe, T. Itoh, A. Muto, Ken Ichi Arai, S. Nimer

Research output: Contribution to journalArticlepeer-review

Abstract

The human GM-CSF recepior (hGMR) consists of a and βsubunits and transmits signals for actwation of early response genes, protein tyrosine phosphorylation. and proliferation in response to hGM-CSF. Mutaliorial analysis of the hGMRβ sutnmit showed that the membrane proximal region and multiple lyr residues are involved in c-fos activation. We investigated the roles of the 8 tyr residues in the βsubunit cytoplasmic domain by phenyaianine subsitution. A mutant βsubunit with all tyr residues converted to Phe can activate both JAK2 and STAT5 but not c-fos. She, or PTP1D. A series of experiments using mutant βsubunits, each of which contains only a single intact Tyr residue, showed that any one of the four middle Tyr is sufficient to transduce signal for activation of c-fos gene. Mutants, having only a single mulated tyr with the remaining tyr residues intact activate the c-fos gene, suggesting that all individual tyr residues are dispensable for c-fos activation. Thus the hGMRβ cytoplasmic domain contains four functionally redundant tyrosine residues. Using dominant negative JAK I and JAK2, we found an essential role for J AK2 but not JAK1 in induction of hGMRβ phosphorylation and subsequent signaling events. However, chimeric hGMRs (|o/β. β/a] or (a/β, β]) do not mediate JAK2 phosphorylation/activation, even though they can transduce hGM-CSF signals. These chimeric receptors induce phosphorylation of JAK1, STAT5, and PTP1D, but not She. Thus for chimeric hGMR, JAK2 activation was required for hGM-CSF-induced She phosphorylation but not other activities.

Original languageEnglish (US)
Number of pages1
JournalExperimental Hematology
Volume24
Issue number9
StatePublished - Dec 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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