Mj. Quon et al., EFFECTS OF OVEREXPRESSING WILD-TYPE AND MUTANT PDGF RECEPTORS ON TRANSLOCATION OF GLUT4 IN TRANSFECTED RAT ADIPOSE-CELLS, Biochemical and biophysical research communications, 226(3), 1996, pp. 587-594
Activation of phosphatidylinositol 3-kinase (PI3K) by insulin is neces
sary for the effect of insulin to recruit GLUT4 to the cell surface in
insulin target cells. In adipose cells, stimulation of endogenous PDG
F receptors (PDGF-R) results in increased PI3K activity without causin
g recruitment of GLUT4. We overexpressed wild-type or mutant forms of
the PDGF-R in rat adipose cells and examined their effects on PDGF- an
d insulin-stimulated recruitment of co-transfected epitope-tagged GLUT
4. Control cells expressing only tagged GLUT4 had a 3-fold increase in
cell surface GLUT4 upon insulin stimulation but no response to PDGF.
Cells overexpressing wild-type PDGF-R maintained insulin responsivenes
s and, in addition, acquired the ability to recruit GLUT4 in response
to PDGF. Surprisingly, overexpression of F740/ F751 (mutant PDGF-R una
ble to directly activate PI3K) led to similar results. Nevertheless, w
ortmannin (an inhibitor of PI3K) blocked effects of both PDGF and insu
lin to recruit GLUT4. Our data suggest that overexpression of PDGF-R m
ediates positive effects on GLUT4 translocation by a wortmannin sensit
ive pathway not dependent on direct interaction of the PDGF-R with PI3
K. (C) 1996 Academic Press, Inc.