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

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 chemoattractant¹. Upon stimulation, the tyrosine kinase PDGF receptor-β (PDGFR-β) autophosphorylates² and forms a complex that includes SH2(Src homology 2)-domain-containing proteins such as the phosphatidylinositol-specific phospholipase C-γ (ref. 3), Ras-GTPase-activating protein (GAP)⁴, and phosphatidylinosi-tol-3-OH kinase⁵. Specific tyrosine-to-phenylalanine substitutions in the PDGFR-β can prevent binding of one SH2-domain-containing protein without affecting binding of other receptor-associated proteins^6,7. Here we use phospholipase C-γ (ref. 8) and PDGFR-β mutants^9-11 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-γ and phosphatidylinositol-3-OH kinase) and migration-suppressing (GAP) activities are recruited by the PDGFR-β to drive chemotaxis towards PDGF-BB.