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Three conserved motifs in the extracellular domain of the human
granulocyte-macrophage colony-stimulating factor receptor subunit are
essential for ligand binding and surface expression
PD Doshi and JF DiPersio
Department of Hematology, University of Rochester, NY.
The receptor for the human granulocyte-macrophage colony-stimulating factor
(GM-CSF) (GM-R) is a heterodimeric complex consisting of two subunits, GM-R
alpha and GM-R beta. Structural analyses have shown a number of highly
conserved amino acid motifs present in both GM-R alpha and GM-R beta. These
motifs include QYFLY, CXW, XW, and WSXWS motifs in the extracellular
domain; a conserved cysteine in the transmembrane domain; and the entire
cytoplasmic domain, including the LXVLX box in the carboxy terminal region
of the cytoplasmic domain. We have investigated the role of these motifs in
GM-R alpha by examining the effects of specific motif mutations on ligand
binding and surface expression. Transient expression of these mutant GM-R
alpha subunits in COS cells shows that these extracellular motis are
essential for ligand binding. Alterations of the cytoplasmic region of GM-R
alpha do not alter GM-CSF binding or the reconstitution of high-affinity
receptors when coexpressed with GM-R beta. Permeabilization and
immunostaining of cells transfected with mutant GM-R alpha subunits yields
data suggesting that each of the mutant subunits is present in the
cytoplasm. Immunostaining of both intact and permeabilized COS cells
transiently transfected with wild-type or mutant GM-R alpha s showed that
extracellular domain mutants accumulated in the cytoplasm and were not
efficiently transported to the cell surface.
Volume 84,
Issue 8,
pp. 2539-2553,
10/15/1994
Copyright © 1994 by The American Society of Hematology
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