Regulation of chemotaxis by the platelet-derived growth factor receptor-beta

Nature. 1994 Feb 3;367(6462):474-6. doi: 10.1038/367474a0.


Chemotaxis is an important component of wound healing, development, immunity and metastasis, yet the signalling pathways that mediate chemotaxis are poorly understood. Platelet-derived growth factor (PDGF) acts both as a mitogen and a chemoattractant. Upon stimulation, the tyrosine kinase PDGF receptor-beta (PDGFR-beta) autophosphorylates and forms a complex that includes SII2(Src homology 2)-domain-containing proteins such as the phosphatidylinositol-specific phospholipase C-gamma, Ras-GTPase-activating protein (GAP), and phosphatidylinositol-3-OH kinase. Specific tyrosine-to-phenylalanine substitutions in the PDGFR-beta can prevent binding of one SH2-domain-containing protein without affecting binding of other receptor-associated proteins. Here we use phospholipase C-gamma and PDGFR-beta mutants to map specific tyrosines involved in both positive and negative regulation of chemotaxis towards the PDGF-BB homodimer. Our results indicate that a delicate balance of migration-promoting (phospholipase C-gamma and phosphatidylinositol-3-OH kinase) and migration-suppressing (GAP) activities are recruited by the PDGFR-beta to drive chemotaxis towards PDGF-BB.

MeSH terms

  • 3T3 Cells
  • Animals
  • Becaplermin
  • CHO Cells
  • Cattle
  • Cell Line
  • Chemotaxis / physiology*
  • Cricetinae
  • GTPase-Activating Proteins
  • Humans
  • Mice
  • Mutation
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Platelet-Derived Growth Factor / metabolism
  • Proteins / metabolism
  • Proto-Oncogene Proteins c-sis
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptors, Platelet-Derived Growth Factor / metabolism
  • Receptors, Platelet-Derived Growth Factor / physiology*
  • Recombinant Proteins / metabolism
  • Type C Phospholipases / metabolism
  • Tyrosine / metabolism
  • ras GTPase-Activating Proteins


  • GTPase-Activating Proteins
  • Platelet-Derived Growth Factor
  • Proteins
  • Proto-Oncogene Proteins c-sis
  • Recombinant Proteins
  • ras GTPase-Activating Proteins
  • Becaplermin
  • Tyrosine
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor)
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Platelet-Derived Growth Factor
  • Type C Phospholipases