Conservation in sequence and affinity of human and rodent PDGF ligands and receptors.

Platelet-derived growth factor (PDGF) consists of two chains, PDGF-A and -B, which activate as homo- or heterodimers two receptors, alpha and beta. To test PDGF function in vivo we have generated neutralizing monoclonal antibodies. When analyzed with rat PDGFs only antibodies raised against human PDGF-AA showed cross-species activity. This correlated with complete amino acid sequence conservation of PDGF-A whereas rat PDGF-B differed in six positions when cloned rat PDGF cDNAs were compared with their human homologs within the receptor binding region. Extracellular domains of cloned rat PDGF alpha- and beta-receptor cDNAs did not reflect this difference in cross-species ligand conservation. When rat extracellular domains were expressed as soluble proteins they bound human PDGF-BB with high affinity after immobilization of the purified proteins on solid phase. Dissociation constants were identical to those of their human homologs. Thus, high affinity binding of human PDGF-BB to extracellular domains does not depend on species origin but only on receptor type.