Identification of a viability domain in the granulocyte/macrophage colony-stimulating factor receptor β-chain involving tyrosine-750

Roger C. Inhorn, Nadia Carlesso, Melissa Durstin, David A. Frank, James D. Griffin

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50 Scopus citations

Abstract

The granulocyte/macrophage colonystimulating factor (GM-CSF) receptor (GMR) is a heterodimeric receptor expressed by myeloid lineage cells. In this study we have investigated domains of the GMR β-chain (GMRβ) involved in maintaining cellular viability. Using a series of nested GMRβ deletion mutants, we demonstrate that there are at least two domains of GMRβ that contribute to viability signals. Deletion of amino acid residues 626-763 causes a viability defect that can be rescued with fetal calf serum (FCS). Deletion of residues 518-626, in contrast, causes a further decrement in viability that can be only partially compensated by the addition of FCS. GMRβ truncated proximal to amino acid 517 will not support long-term growth under any conditions. Site-directed mutagenesis of tyrosine-750 (Y750), which is contained within the distal viability domain, to phenylalanine eliminates all demonstrable tyrosine phosphorylation of GMRβ. Cell lines transfected with mutant GMRβ (Y750 → F) have a viability disadvantage when compared to cell lines containing wild-type GMR that is partially rescued by the addition of FCS. We studied signal transduction in mutant cell lines in an effort to identify pathways that might participate in the viability signal. Although tyrosine phosphorylation of JAK2, SHPTP2, and Vav is intact in Y750 → F mutant cell lines, Shc tyrosine phosphorylation is reduced. This suggests a potential role for Y750 and potentially She in a GM-CSF-induced signaling pathway that helps maintain cellular viability.

Original languageEnglish (US)
Pages (from-to)8665-8669
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number19
DOIs
StatePublished - Sep 12 1995

ASJC Scopus subject areas

  • General

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