J Biol Chem 1993 Oct 25;26830:22814-9.

Dominant-negative mutations of platelet-derived growth factor (PDGF) receptors. Inhibition of receptor function by ligand-dependent formation of heterodimers between PDGF alpha- and beta-receptors.

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We showed previously that a truncated form of the platelet-derived growth factor (PDGF) beta-receptor lacking its kinase region can form a nonfunctional heterodimer with the wild-type beta-receptor and thereby inhibit its signal transduction. In this paper we investigated whether the truncated form of either alpha- or beta-receptor could block the function of the other type of wild-type PDGF receptor. When the truncated alpha-receptor was expressed in Xenopus oocytes in excess over either the wild-type alpha- or beta-receptor, the Ca2+ mobilization signal elicited by either the wild-type alpha- or beta-receptor was completely blocked. The truncated beta-receptor abolished signaling by the wild-type alpha-receptor in response to PDGF-AB or -BB. However signal transduction by the alpha-receptor in response to PDGF-AA was not affected by the truncated beta-receptor. In the presence of PDGF-AB or -BB, both the wild-type and truncated beta-receptors formed a heterologous complex with the alpha-receptor in intact cells. A kinase-inactive beta-receptor (an ATP-binding site mutation) became cross-phosphorylated on tyrosine residues by the co-expressed wild-type alpha-receptor in response to PDGF-AB or -BB but not in response to PDGF-AA. These findings indicate that the alpha-and beta-receptors interact in response to PDGF-AB or -BB and are consistent with the hypothesis that the truncated alpha-receptor inhibits function of the wild-type beta-receptor through formation of a ligand-dependent nonfunctional alpha beta-heterodimer. A similar heterodimer can form between the truncated beta-receptor and the wild-type alpha-receptor. These observations provide useful information for future studies using dominant-negative mutations of PDGF receptors to selectively inhibit the actions of specific PDGFs in animals.

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Species referenced: Xenopus
Genes referenced: pdgfa