THE COLONY-STIMULATING FACTORS AND MOLECULAR-TRANSPORT

Glucose is fundamental to the metabolism and survival of mammalian cel ls, and its passage across cell membranes is mediated by a family of t ransport proteins (glucose transporters) located at the cell membrane. We studied the regulation of glucose transport by granulocyte-macroph age colony-stimulating factor (GM-CSF), a hemopoietin that functions i n regulating the proliferation, differentiation, maturation acid survi val of cells of the host defense system. The receptor for GM-CSF is co mposed 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 hum an GM-CSF receptor a subunit, we provided direct evidence indicating t hat the isolated alpha subunit signals for increased glucose uptake in a phosphorylation-independent manner. We extended these studies to hu man neutrophils and HL-60 cells and found that signaling for hexose up take also occurs in a phosphorylation-independent manner in cells expr essing the high-affinity GM-CSF receptor. Since the glucose transporte rs are multifunctional transport proteins, the findings regarding GM-C SF regulation of cellular glucose uptake may have wide import relative to CSF regulation of molecular transport in target cells.