Identification of a hydrophobic region in the carboxyl terminus of the platelet-derived growth factor beta-receptor which is important for ligand-mediated endocytosis

J Biol Chem. 1991 Nov 5;266(31):21158-64.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Division / drug effects
  • Cell Line
  • DNA Mutational Analysis
  • Down-Regulation
  • Endocytosis
  • Molecular Sequence Data
  • Phosphorylation
  • Platelet-Derived Growth Factor / metabolism
  • Protein-Tyrosine Kinases / metabolism
  • Receptors, Cell Surface / chemistry*
  • Receptors, Cell Surface / metabolism
  • Receptors, Platelet-Derived Growth Factor
  • Solubility
  • Structure-Activity Relationship
  • Swine
  • Transfection

Substances

  • Platelet-Derived Growth Factor
  • Receptors, Cell Surface
  • Protein-Tyrosine Kinases
  • Receptors, Platelet-Derived Growth Factor