title: Identification of a hydrophobic region in the carboxyl terminus of the platelet-derived growth factor beta-receptor which is important for ligand-mediated endocytosis.
abstract: The functional properties of carboxyl terminally truncated mutants of the platelet-derived growth factor beta-receptor were compared with those of the wild-type receptor and a receptor mutant made kinase negative by a point mutation. A mutant in which 98 amino acids were deleted retained kinase activity and mediated a mitogenic signal, whereas deletion of 141 or 155 amino acids led to loss of kinase activity and ability to mediate a mitogenic signal. The mutant with 155 amino acids deleted, i.e. the entire carboxyl-terminal tail downstream of the kinase domain, did not undergo ligand-mediated internalization and down-regulation, whereas the mutant with 141 amino acids deleted was internalized at a relatively high rate. This indicates that the 14 amino acids immediately downstream of the kinase domain is of importance for the internalization of the platelet-derived growth factor beta-receptor. This region is hydrophobic and shares no similarity to other sequences postulated to mediate endocytotic signals.
authors.affiliation: Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Mori
authors.forename: L
authors.initials: L
authors.lastname: Claesson-Welsh
authors.forename: C H
authors.initials: CH
authors.lastname: Heldin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004252:DNA Mutational Analysis; D015536:Down-Regulation; D004705:Endocytosis; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor; D012995:Solubility; D013329:Structure-Activity Relationship; D013552:Swine; D014162:Transfection
chemical_list: D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor