Regulation of chemotaxis by the platelet-derived growth factor receptor-beta - PubMed (original) (raw)

. 1994 Feb 3;367(6462):474-6.

doi: 10.1038/367474a0.

Affiliations

• PMID: 8107807
• DOI: 10.1038/367474a0

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

V Kundra et al. Nature. 1994.

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.

PubMed Disclaimer

Similar articles

• Platelet-derived growth factor-dependent activation of phosphatidylinositol 3-kinase is regulated by receptor binding of SH2-domain-containing proteins which influence Ras activity.
  Klinghoffer RA, Duckworth B, Valius M, Cantley L, Kazlauskas A. Klinghoffer RA, et al. Mol Cell Biol. 1996 Oct;16(10):5905-14. doi: 10.1128/MCB.16.10.5905. Mol Cell Biol. 1996. PMID: 8816504 Free PMC article.
• Mutation of a Src phosphorylation site in the PDGF beta-receptor leads to increased PDGF-stimulated chemotaxis but decreased mitogenesis.
  Hansen K, Johnell M, Siegbahn A, Rorsman C, Engström U, Wernstedt C, Heldin CH, Rönnstrand L. Hansen K, et al. EMBO J. 1996 Oct 1;15(19):5299-313. EMBO J. 1996. PMID: 8895575 Free PMC article.
• Platelet derived growth factor/tyrosine kinase receptor mediated proliferation.
  Benito M, Lorenzo M. Benito M, et al. Growth Regul. 1993 Sep;3(3):172-9. Growth Regul. 1993. PMID: 8220110 Review.
• Mechanisms of platelet-derived growth factor-induced chemotaxis.
  Rönnstrand L, Heldin CH. Rönnstrand L, et al. Int J Cancer. 2001 Mar 15;91(6):757-62. doi: 10.1002/1097-0215(200002)9999:9999<::aid-ijc1136>3.0.co;2-j. Int J Cancer. 2001. PMID: 11275976 Review. No abstract available.

Cited by

• Site-selective regulation of platelet-derived growth factor beta receptor tyrosine phosphorylation by T-cell protein tyrosine phosphatase.
  Persson C, Sävenhed C, Bourdeau A, Tremblay ML, Markova B, Böhmer FD, Haj FG, Neel BG, Elson A, Heldin CH, Rönnstrand L, Ostman A, Hellberg C. Persson C, et al. Mol Cell Biol. 2004 Mar;24(5):2190-201. doi: 10.1128/MCB.24.5.2190-2201.2004. Mol Cell Biol. 2004. PMID: 14966296 Free PMC article.
• Disruption of PDGFRalpha-initiated PI3K activation and migration of somite derivatives leads to spina bifida.
  Pickett EA, Olsen GS, Tallquist MD. Pickett EA, et al. Development. 2008 Feb;135(3):589-98. doi: 10.1242/dev.013763. Development. 2008. PMID: 18192285 Free PMC article.
• The chemotactic response to PDGF-BB: evidence of a role for Ras.
  Kundra V, Anand-Apte B, Feig LA, Zetter BR. Kundra V, et al. J Cell Biol. 1995 Aug;130(3):725-31. doi: 10.1083/jcb.130.3.725. J Cell Biol. 1995. PMID: 7622571 Free PMC article.
• The GTPase-activating protein of Ras suppresses platelet-derived growth factor beta receptor signaling by silencing phospholipase C-gamma 1.
  Valius M, Secrist JP, Kazlauskas A. Valius M, et al. Mol Cell Biol. 1995 Jun;15(6):3058-71. doi: 10.1128/MCB.15.6.3058. Mol Cell Biol. 1995. PMID: 7760802 Free PMC article.
• GRB2 stabilizes RAD51 at reversed replication forks suppressing genomic instability and innate immunity against cancer.
  Ye Z, Xu S, Shi Y, Cheng X, Zhang Y, Roy S, Namjoshi S, Longo MA, Link TM, Schlacher K, Peng G, Yu D, Wang B, Tainer JA, Ahmed Z. Ye Z, et al. Nat Commun. 2024 Mar 8;15(1):2132. doi: 10.1038/s41467-024-46283-y. Nat Commun. 2024. PMID: 38459011 Free PMC article.

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Nature Publishing Group

• Molecular Biology Databases

  • Mouse Genome Informatics (MGI)

• Miscellaneous

  • NCI CPTAC Assay Portal