Ligand activation causes a phosphorylation-dependent change in platelet-derived growth factor receptor conformation. 
The effect of ligand binding on PDGF receptor conformation was examined using peptide antisera directed against specific receptor domains.  Antiserum 83, which recognizes the receptor's carboxyl terminus, preferentially immunoprecipitated the ligand-activated form of the PDGF receptor from 35S-labeled BALB/c 3T3 cells.  By contrast, two antisera directed against other receptor sequences precipitated unactivated and activated receptors equally well.  Denatured receptors were recognized equally by all antisera, even 83.  Thus, ligand activation caused a change in PDGF receptor conformation that enhanced accessibility of the receptor was induced by the three different forms of PDGF (AA and BB homodimers and AB heterodimer) and was reversed by suramin, a polyanionic compound that dissociates PDGF from the receptor.  The inhibitory effect of suramin on receptor conformation was abolished by the phosphatase inhibitor sodium orthovanadate, suggesting that receptor phosphorylation mediated the conformational change.  In a cell-free assay, the change in receptor conformation was induced by PDGF only in the presence of ATP and was inhibited by AMP-PNP, a nonhydrolyzable analog of ATP.  The functional significance of receptor conformation was examined in CHO fibroblasts transfected with wild type or mutated forms of the PDGF receptor.  When receptor tyrosine kinase activity was abolished by a mutation of the ATP binding site, the receptor no longer underwent PDGF-induced conformational change and did not mediate PDGF-induced mitogenesis, even though [125I]PDGF binding was normal.  Ligand-induced receptor autophosphorylation was reduced but present in cells expressing receptors that lacked a major site of autophosphorylation and was present in cells expressing receptors that lacked the kinase insert domain.(ABSTRACT TRUNCATED AT 250 WORDS)