STRUCTURAL BASIS FOR THE EXTRACELLULAR RETENTION OF PDGF A-CHAIN USING A SYNTHETIC PEPTIDE CORRESPONDING TO EXON-6

Alternative splicing of PDGF A-chain exon 6 yields two species that di ffer by a highly conserved cationic carboxyl-terminus consisting of 18 amino acid residues (A194-211). Previous findings have demonstrated t hat a synthetic peptide representing A194-211 binds to cultured cells and interferes with the binding and biological activity of several pol ypeptide growth factors. We now demonstrate that the peptide, which bi nds to the extracellular matrix in a specific and glycosaminoglycan-de pendent manner, can also inhibit the binding of basic FGF to the matri x. The cellular retention signal encoded by exon 6 accounts for differ ences in the mitogenic responsiveness to conditioned media from Chines e hamster ovary cells transfected with the cDNA for the long and short splice forms of the PDGF A-chain. That the PDGF A-chain exon 6 produc t may share anionic binding sites with a matrix-resident polypeptide g rowth factor in the extracellular matrix suggests a role for A194-211 in the storage of PDGF bearing this sequence.