A critical role for the cytoplasmic domain of the granulocyte-macrophage colony-stimulating factor alpha receptor in mediating cell growth.

A. Polotskaya, Y. Zhao, M. L. Lilly, A. S. Kraft

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

The human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor is composed of an alpha subunit which binds GM-CSF and a beta subunit which allows for high affinity binding. To investigate the role of the short cytoplasmic tail (54 amino acids) of the alpha receptor in mediating signal transduction and in controlling cell growth, we placed a stop codon after the alpha receptor transmembrane domain and expressed this receptor in murine Ba/F3 cells. Unlike the complete alpha subunit, this shortened receptor was unable to stimulate protein phosphorylation or mediate entry into the cell cycle. By comparing Ba/F3 cells expressing the alpha and beta receptors with those expressing the alpha or the terminated alpha receptor, we have been able to correlate specific GM-CSF-induced events with cell cycle commitment. We find that cell growth is correlated with prolonged increases in the cell levels of c-myc, pim-1, and cyclin D2 mRNAs, but not with changes in either immediate early genes or mitogen-activated protein kinase phosphorylation. This suggests that additional signal transduction pathways not mediated by known phosphoproteins are activated by GM-CSF. Since the beta receptor is shared by human interleukins 3 and 5, our data suggest that the specificity of response to GM-CSF is mediated in part by the short cytoplasmic tail of the alpha receptor subunit.

Original languageEnglish (US)
Pages (from-to)523-531
Number of pages9
JournalCell growth & differentiation : the molecular biology journal of the American Association for Cancer Research
Volume4
Issue number6
StatePublished - Jun 1993
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'A critical role for the cytoplasmic domain of the granulocyte-macrophage colony-stimulating factor alpha receptor in mediating cell growth.'. Together they form a unique fingerprint.

Cite this