title: Characterization of the retention motif in the C-terminal part of the long splice form of platelet-derived growth factor A-chain.
abstract: Platelet-derived growth factor (PDGF) A-chain is found in two different splice variants; the long A-chain variant differs from the short one in that it contains a stretch of basic amino acid residues in the C-terminal part that mediates retention of the growth factor inside the producer cell and to the cell matrix. By analyzing mutants in which different amino acid residues in the retention motif had been changed to alanine residues, we found that the total positive charge of the sequence is of importance for the function of the retention motif. Moreover, we showed that retention also occurs if only one of the polypeptides in the PDGF dimer carries the retention motif. Surface iodination and competition with a peptide having the sequence of the retention motif revealed that the long A-chain variant, in contrast to the short A-chain variant, is localized on the outside of the cells and is also associated to the cell matrix. The association is likely to be mediated partially through heparan sulfate proteoglycans since treatment of matrix with heparitinase released the long A-chain variant.
authors.affiliation: Ludwig Institute for Cancer Research, Uppsala, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Andersson
authors.forename: A
authors.initials: A
authors.lastname: Ostman
authors.forename: B
authors.initials: B
authors.lastname: Westermark
authors.forename: C H
authors.initials: CH
authors.lastname: Heldin
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D002451:Cell Compartmentation; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007526:Isoelectric Point; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship
chemical_list: D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; C075278:platelet-derived growth factor A