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

Watanabe, T. Itoh, A. Muto, Ken Ichi Arai, Stephen D Nimer

Research output: Contribution to journalArticle

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)
Pages (from-to)1108
Number of pages1
JournalExperimental Hematology
Volume24
Issue number9
StatePublished - 1996
Externally publishedYes

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Granulocyte-Macrophage Colony-Stimulating Factor
Tyrosine
Signal Transduction
Phosphorylation
fos Genes
Membranes
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

Roles of tyrosine phosphorylalion and JAK2 in hGM-CSF signal transduction S. / Watanabe; Itoh, T.; Muto, A.; Arai, Ken Ichi; Nimer, Stephen D.

In: Experimental Hematology, Vol. 24, No. 9, 1996, p. 1108.

Research output: Contribution to journalArticle

Watanabe, Itoh, T, Muto, A, Arai, KI & Nimer, SD 1996, 'Roles of tyrosine phosphorylalion and JAK2 in hGM-CSF signal transduction S', Experimental Hematology, vol. 24, no. 9, pp. 1108.
Watanabe ; Itoh, T. ; Muto, A. ; Arai, Ken Ichi ; Nimer, Stephen D. / Roles of tyrosine phosphorylalion and JAK2 in hGM-CSF signal transduction S. In: Experimental Hematology. 1996 ; Vol. 24, No. 9. pp. 1108.
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