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 differ by a highly conserved cationic carboxyl-terminus consisting of 18 amino acid residues (A194-211). Previous findings have demonstrated that a synthetic peptide representing A194-211 binds to cultured cells and interferes with the binding and biological activity of several polypeptide growth factors. We now demonstrate that the peptide, which binds to the extracellular matrix in a specific and glycosaminoglycan-dependent manner, can also inhibit the binding of basic FGF to the matrix. The cellular retention signal encoded by exon 6 accounts for differences in the mitogenic responsiveness to conditioned media from Chinese 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 product may share anionic binding sites with a matrix-resident polypeptide growth factor in the extracellular matrix suggests a role for A194-211 in the storage of PDGF bearing this sequence.
University of New South Wales Center for Thrombosis and Vascular Research, Prince of Wales Hospital, Sydney, Australia.
L M
LM
Khachigian
C N
CN
Chesterman
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D016466:CHO Cells; D006224:Cricetinae; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D006025:Glycosaminoglycans / Q000494:pharmacology; D007457:Iodine Radioisotopes; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics; D010982:Platelet-Derived Growth Factor / Q000737:chemistry* / Q000235:genetics; D011509:Proteoglycans / Q000378:metabolism; D011869:Radioligand Assay; D013329:Structure-Activity Relationship; D013462:Sulfur Radioisotopes; D014162:Transfection
D018076:DNA, Complementary; D006025:Glycosaminoglycans; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D010982:Platelet-Derived Growth Factor; D011509:Proteoglycans; D013462:Sulfur Radioisotopes; C075278:platelet-derived growth factor A; C087967:platelet-derived growth factor A (194-211)