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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucose is fundamental to the metabolism and survival of mammalian cells, and its passage across cell membranes is mediated by a family of transport proteins (glucose transporters) located at the cell membrane. We studied the regulation of glucose transport by granulocyte-macrophage colony-stimulating factor (GM-CSF), a hemopoietin that functions in regulating the proliferation, differentiation, maturation and survival of cells of the host defense system. The receptor for GM-CSF is composed of an alpha and beta subunit, and the alpha-beta complex binds GM-CSF with high affinity whereas the isolated alpha subunit binds GM-CSF with low affinity. Using Xenopus laevis oocytes expressing the human GM-CSF receptor alpha subunit, we provided direct evidence indicating that the isolated alpha subunit signals for increased glucose uptake in a phosphorylation-independent manner. We extended these studies to human neutrophils and HL-60 cells and found that signaling for hexose uptake also occurs in a phosphorylation-independent manner in cells expressing the high-affinity GM-CSF receptor. Since the glucose transporters are multifunctional transport proteins, the findings regarding GM-CSF regulation of cellular glucose uptake may have wide import relative to CSF regulation of molecular transport in target cells.
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PMID:The colony-stimulating factors and molecular transport. 769 70

The receptor for granulocyte-macrophage colony-stimulating factor (GM-CSF) is composed of an alpha and beta subunit, which together form the high-affinity receptor. The alpha subunit by itself binds ligand at low affinity, whereas the isolated beta subunit does not bind GM-CSF. It is generally believed that the high-affinity receptor is responsible for the multiple functions of GM-CSF and that the isolated alpha subunit (GMR alpha) does not transduce a signal. Xenopus laevis oocytes injected with RNA encoding human GMR alpha expressed up to 10(10) low-affinity sites for GM-CSF (Kd = 6 nM). GM-CSF binding to the alpha subunit expressed in Xenopus oocytes caused activation of 2-deoxyglucose transport through endogenous glucose transporters. 2-Deoxyglucose transport was stimulated by similar low concentrations of GM-CSF in HL-60 leukemia cells as well as normal human neutrophils and Xenopus oocytes expressing GMR alpha. Engagement of the isolated alpha subunit in oocytes did not lead to protein phosphorylation or tyrosine phosphorylation of mitogen-activated protein kinase (MAP kinase). Staurosporin and genistein inhibited GM-CSF-induced tyrosine phosphorylation of MAP kinase in human neutrophils and HL-60 cells without affecting GM-CSF-stimulated uptake of 2-deoxyglucose. These results provide direct evidence that the isolated alpha subunit signals for hexose transport and can do so without engagement of the kinase cascade. Our data also indicate that signaling for hexose uptake may occur in a phosphorylation-independent manner in cells expressing the high-affinity GM-CSF receptor.
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PMID:The alpha subunit of the human granulocyte-macrophage colony-stimulating factor receptor signals for glucose transport via a phosphorylation-independent pathway. 814 50