The colony-stimulating factors and molecular transport.
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.
Golde
D W
DW
Memorial Sloan-Kettering Cancer Center, New York, New York.
Ding
D X
DX
Rivas
C I
CI
Vera
J C
JC
D000818:Animals; D001693:Biological Transport, Active; D002460:Cell Line; D005260:Female; D015870:Gene Expression; D019833:Genistein; D005947:Glucose / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007529:Isoflavones / Q000494:pharmacology; D008954:Models, Biological; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014982:Xenopus laevis
D007529:Isoflavones; D009004:Monosaccharide Transport Proteins; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D005947:Glucose