Two Different Subunits Associate to Create Isoform-Specific Platelet-derived Growth Factor Receptors

TLDR

PDGF receptors exist in multiple forms that differ in their specificity for the PDGF isoforms A and B. The study investigates whether high‑affinity PDGF binding requires a heterodimer of an alpha subunit (binding A or B) and a beta subunit (binding only B). In the absence of ligand, the alpha and beta subunits are either free or form rapidly reversible complexes. Alpha and beta subunits are similar in size but differ in binding specificity and can be distinguished by antibody PR7212; ligand binding induces a high‑affinity heterodimer, and subunit abundance varies by cell type, correlating with mitogenic sensitivity to PDGF isoforms.

Abstract

Abstract Recent evidence has demonstrated that there is more than one form of platelet-derived growth factor (PDGF) receptor and that these receptors differ in their specificity for the multiple isoforms of PDGF. We present evidence that high affinity binding of PDGF requires association of two different receptor subunits: an alpha-subunit that can bind either a B- or an A-chain of PDGF, and a beta-subunit that can bind only a B-chain. The alpha- and beta-subunits appear to be similar in size but can be distinguished by binding specificity and by an antireceptor monoclonal antibody, PR7212, which recognizes only the beta-subunit. In the absence of PDGF, these subunits either exist separately or form rapidly reversible complexes. In the presence of PDGF, receptor subunits of appropriate specificity interact with a PDGF molecule to form a high affinity complex. Both the absolute and relative numbers of these two PDGF receptor subunits vary on different cell types and correspond to differences in the mitogenic sensitivity of cells to the different PDGF isoforms.