Inhibition of PDGF beta receptor signal transduction by coexpression of a truncated receptor.
A mutated form of the platelet-derived growth factor (PDGF) beta receptor lacking most of its cytoplasmic domain was tested for its ability to block wild-type PDGF receptor function. PDGF induced the formation of complexes consisting of wild-type and truncated receptors. Such complexes were defective in autophosphorylation. When truncated receptors were expressed in excess compared to wild-type receptors, stimulation by PDGF of receptor autophosphorylation, association of phosphatidylinositol-3 kinase with the receptor, and calcium mobilization were blocked. Thus, a truncated receptor can inactivate wild-type receptor function by forming ligand-dependent receptor complexes (probably heterodimers) that are incapable of mediating the early steps of signal transduction.
Ueno
H
H
Department of Medicine, University of California, San Francisco 94143.
Colbert
H
H
Escobedo
J A
JA
Williams
L T
LT
D000818:Animals; D002478:Cells, Cultured; D002499:Centrifugation, Density Gradient; D006224:Cricetinae; D066298:In Vitro Techniques; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors* / Q000502:physiology; D017479:Receptors, Platelet-Derived Growth Factor; D015398:Signal Transduction / Q000502:physiology*
D008024:Ligands; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D017479:Receptors, Platelet-Derived Growth Factor