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.