Regulation of chemotaxis by the platelet-derived growth factor receptor-β
- 1 February 1994
- journal article
- Published by Springer Nature in Nature
- Vol. 367 (6462), 474-476
- https://doi.org/10.1038/367474a0
Abstract
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.Keywords
This publication has 22 references indexed in Scilit:
- Tyrosines 1021 and 1009 are phosphorylation sites in the carboxy terminus of the platelet-derived growth factor receptor beta subunit and are required for binding of phospholipase C gamma and a 64-kilodalton protein, respectively.Molecular and Cellular Biology, 1993
- Distinct phosphotyrosines on a growth factor receptor bind to specific molecules that mediate different signaling pathwaysCell, 1992
- PDGF stimulation of inositol phospholipid hydrolysis requires PLC-γ1 phosphorylation on tyrosine residues 783 and 1254Cell, 1991
- Platelet-derived growth factor (PDGF)-dependent association of phospholipase C-gamma with the PDGF receptor signaling complex.Molecular and Cellular Biology, 1990
- PDGF β-receptor stimulates tyrosine phosphorylation of GAP and association of GAP with a signaling complexCell, 1990
- Platelet-derived growth factor (PDGF) binding promotes physical association of PDGF receptor with phospholipase C.Proceedings of the National Academy of Sciences, 1989
- Role of Phosphatidylinositol Kinase in PDGF Receptor Signal TransductionScience, 1989
- A PDGF receptor domain essential for mitogenesis but not for many other responses to PDGFNature, 1988
- Platelet-derived growth factor in chemotactic for fibroblasts.The Journal of cell biology, 1982
- THE CHEMOTACTIC EFFECT OF MIXTURES OF ANTIBODY AND ANTIGEN ON POLYMORPHONUCLEAR LEUCOCYTESThe Journal of Experimental Medicine, 1962