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

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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 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 proteins6,7. Here we use phospholipase C-γ (ref. 8) and PDGFR-β mutants9–11 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.

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Author notes

  1. Bruce R. Zetter: To whom correspondence should be addressed

Authors and Affiliations

  1. Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts, 02115, USA

    Vikas Kundra & Bruce R. Zetter

  2. Department of Medicine, Cardiovascular Research Institute, Howard Hughes Medical Institute, University of California, San Francisco, California, 94143, USA

    Jaime A. Escobedo & Lewis T. Williams

  3. National Jewish Center for Immunology and Respiratory Medicine, 1400 Jackson Street, Denver, Colorado, 80206, USA

    Andrius Kazlauskas

  4. Laboratory of Biochemistry, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA

    Ha Kun Kim & Sue Goo Rhee

Authors
  1. Vikas Kundra
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  2. Jaime A. Escobedo
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  3. Andrius Kazlauskas
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  4. Ha Kun Kim
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  5. Sue Goo Rhee
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  6. Lewis T. Williams
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  7. Bruce R. Zetter
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Kundra, V., Escobedo, J., Kazlauskas, A. et al. Regulation of chemotaxis by the platelet-derived growth factor receptor-β. Nature 367, 474–476 (1994). https://doi.org/10.1038/367474a0

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  • DOI: https://doi.org/10.1038/367474a0

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