THE GAMMA-SUBUNIT OF THE HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR-RECEPTOR SIGNALS FOR GLUCOSE-TRANSPORT VIA A PHOSPHORYLATION-INDEPENDENT PATHWAY
Dxh. Ding et al., THE GAMMA-SUBUNIT OF THE HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR-RECEPTOR SIGNALS FOR GLUCOSE-TRANSPORT VIA A PHOSPHORYLATION-INDEPENDENT PATHWAY, Proceedings of the National Academy of Sciences of the United Statesof America, 91(7), 1994, pp. 2537-2541
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 l
ow affinity, whereas the isolated beta subunit does not bind GM-CSF. I
t is generally believed that the high-affinity receptor is responsible
for the multiple functions of GM-CSF and that the isolated alpha subu
nit (GMRalpha) does not transduce a signal. Xenopus laevis oocytes inj
ected with RNA encoding human GMRalpha expressed up to 10(10) low-affi
nity sites for GM-CSF (K(d) = 6 nM). GM-CSF binding to the alpha subun
it expressed in Xenopus oocytes caused activation of 2-deoxyglucose tr
ansport through endogenous glucose transporters. 2-Deoxyglucose transp
ort was stimulated by similar low concentrations of GM-CSF in HL-60 le
ukemia cells as well as normal human neutrophils and Xenopus oocytes e
xpressing GMRalpha. Engagement of the isolated alpha subunit in oocyte
s did not lead to protein phosphorylation or tyrosine phosphorylation
of mitogen-activated protein kinase (MAP kinase). Staurosporin and gen
istein inhibited GM-CSF-induced tyrosine phosphorylation of MAP kinase
in human neutrophils and HL-60 cells without affecting GM-CSF-stimula
ted uptake of 2-deoxyglucose. These results provide direct evidence th
at the isolated alpha subunit signals for hexose transport and can do
so without engagement of the kinase cascade. Our data also indicate th
at signaling for hexose uptake may occur in a phosphorylation-independ
ent manner in cells expressing the high-affinity GM-CSF receptor.