A tyrosinated peptide representing the alternatively spliced exon of the platelet-derived growth factor A-chain binds specifically to cultured cells and interferes with binding of several growth factors.
Platelet-derived growth factor (PDGF) is a potent mitogen for cells of mesenchymal origin. Alternative exon splicing is responsible for two forms of the PDGF A-chain which differ at the carboxyl terminus by a highly basic region consisting of 18 amino acids. To clarify the function of the region, we synthesized an octadecapeptide corresponding to this extension (A194-211), incorporated a tyrosine residue at the amino terminus, and used the radioiodinated construct in binding studies with Balb/c3T3 cells and a variety of human cell lines. 125I-(Y)A194-211 bound specifically, reversibly, saturably, and with low affinity to a large population of binding sites on these cells. In addition, (Y)A194-211 markedly reduced the binding of its parent protein, 125I-PDGF-AAL, to its receptor. (Y)A194-211 also attenuated the binding of epidermal growth factor and several other isoforms of PDGF, but did not interfere with the binding of transferrin to its receptor. These observations were not due to competitive binding of peptide directly to known receptors for the respective growth factors, but was likely due to interaction of (Y)A194-211 with extracellular glycosaminoglycan. Thus, A194-211 may represent an additional heparin binding domain on mature PDGF-AAL, and as an isolate, is capable of modulating interactions between several potent growth factors and their respective receptors.
Khachigian
L M
LM
University of New South Wales, Department of Haematology, Prince of Wales Hospital, Randwick, Australia.
Owensby
D A
DA
Chesterman
C N
CN
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D002478:Cells, Cultured; D006224:Cricetinae; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D004730:Endothelium, Vascular / Q000378:metabolism*; D005091:Exons; D006493:Heparin / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D009369:Neoplasms; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism*; D012326:RNA Splicing; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor; D013379:Substrate Specificity; D014443:Tyrosine
D004273:DNA, Neoplasm; D046911:Macromolecular Substances; D010455:Peptides; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D014443:Tyrosine; D006493:Heparin; D017479:Receptors, Platelet-Derived Growth Factor