Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1999 Apr 1;339(Pt 1):11–14.

Gi-mediated tyrosine phosphorylation of Grb2 (growth-factor-receptor-bound protein 2)-bound dynamin-II by lysophosphatidic acid.

O Kranenburg 1, I Verlaan 1, W H Moolenaar 1
PMCID: PMC1220121  PMID: 10085221

Abstract

Lysophosphatidic acid (LPA) is the prototypic G-protein-coupled receptor agonist that activates the Ras-mitogen-activated protein (MAP) kinase cascade through pertussis toxin (PTX)-sensitive Gi and enhanced tyrosine kinase activity. We recently detected a 100 kDa protein (p100) that binds to the C-terminal SH3 domain of growth-factor-receptor-bound protein 2 (Grb2) and becomes tyrosine phosphorylated in a PTX-sensitive manner in LPA-treated Rat-1 cells [Kranenburg, Verlaan, Hordijk and Moolenaar (1997) EMBO J. 16, 3097-3105]. Through glutathione S-transferase-Grb2 affinity purification and microsequencing, we have now identified p100 as dynamin-II, a GTPase that regulates clathrin-mediated endocytosis. We show that in Rat-1 cells, Grb2-bound dynamin-II is rapidly tyrosine phosphorylated in response to LPA in a PTX-sensitive manner. Thus, tyrosine phosphorylation of Grb2-bound dynamin-II may be a critical event in Gi-mediated activation of the Ras-MAP kinase cascade in fibroblasts.

Full Text

The Full Text of this article is available as a PDF (123.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahn S., Maudsley S., Luttrell L. M., Lefkowitz R. J., Daaka Y. Src-mediated tyrosine phosphorylation of dynamin is required for beta2-adrenergic receptor internalization and mitogen-activated protein kinase signaling. J Biol Chem. 1999 Jan 15;274(3):1185–1188. doi: 10.1074/jbc.274.3.1185. [DOI] [PubMed] [Google Scholar]
  2. Baron V., Alengrin F., Van Obberghen E. Dynamin associates with Src-Homology Collagen (Shc) and becomes tyrosine phosphorylated in response to insulin. Endocrinology. 1998 Jun;139(6):3034–3037. doi: 10.1210/endo.139.6.6131. [DOI] [PubMed] [Google Scholar]
  3. Ceresa B. P., Kao A. W., Santeler S. R., Pessin J. E. Inhibition of clathrin-mediated endocytosis selectively attenuates specific insulin receptor signal transduction pathways. Mol Cell Biol. 1998 Jul;18(7):3862–3870. doi: 10.1128/mcb.18.7.3862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Daaka Y., Luttrell L. M., Ahn S., Della Rocca G. J., Ferguson S. S., Caron M. G., Lefkowitz R. J. Essential role for G protein-coupled receptor endocytosis in the activation of mitogen-activated protein kinase. J Biol Chem. 1998 Jan 9;273(2):685–688. doi: 10.1074/jbc.273.2.685. [DOI] [PubMed] [Google Scholar]
  5. Daub H., Weiss F. U., Wallasch C., Ullrich A. Role of transactivation of the EGF receptor in signalling by G-protein-coupled receptors. Nature. 1996 Feb 8;379(6565):557–560. doi: 10.1038/379557a0. [DOI] [PubMed] [Google Scholar]
  6. Floyd S., De Camilli P. Endocytosis proteins and cancer: a potential link? Trends Cell Biol. 1998 Aug;8(8):299–301. doi: 10.1016/s0962-8924(98)01316-6. [DOI] [PubMed] [Google Scholar]
  7. Glenney J. R., Jr, Chen W. S., Lazar C. S., Walton G. M., Zokas L. M., Rosenfeld M. G., Gill G. N. Ligand-induced endocytosis of the EGF receptor is blocked by mutational inactivation and by microinjection of anti-phosphotyrosine antibodies. Cell. 1988 Mar 11;52(5):675–684. doi: 10.1016/0092-8674(88)90405-9. [DOI] [PubMed] [Google Scholar]
  8. Hinshaw J. E., Schmid S. L. Dynamin self-assembles into rings suggesting a mechanism for coated vesicle budding. Nature. 1995 Mar 9;374(6518):190–192. doi: 10.1038/374190a0. [DOI] [PubMed] [Google Scholar]
  9. Kharbanda S., Saleem A., Yuan Z., Emoto Y., Prasad K. V., Kufe D. Stimulation of human monocytes with macrophage colony-stimulating factor induces a Grb2-mediated association of the focal adhesion kinase pp125FAK and dynamin. Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):6132–6136. doi: 10.1073/pnas.92.13.6132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kranenburg O., Verlaan I., Hordijk P. L., Moolenaar W. H. Gi-mediated activation of the Ras/MAP kinase pathway involves a 100 kDa tyrosine-phosphorylated Grb2 SH3 binding protein, but not Src nor Shc. EMBO J. 1997 Jun 2;16(11):3097–3105. doi: 10.1093/emboj/16.11.3097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lamaze C., Schmid S. L. Recruitment of epidermal growth factor receptors into coated pits requires their activated tyrosine kinase. J Cell Biol. 1995 Apr;129(1):47–54. doi: 10.1083/jcb.129.1.47. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lohi O., Lehto V. P. Src phosphorylates EAST, a novel EGF receptor-associated protein. FEBS Lett. 1998 Aug 7;432(3):225–227. doi: 10.1016/s0014-5793(98)00874-6. [DOI] [PubMed] [Google Scholar]
  13. Luttrell L. M., Hawes B. E., van Biesen T., Luttrell D. K., Lansing T. J., Lefkowitz R. J. Role of c-Src tyrosine kinase in G protein-coupled receptor- and Gbetagamma subunit-mediated activation of mitogen-activated protein kinases. J Biol Chem. 1996 Aug 9;271(32):19443–19450. doi: 10.1074/jbc.271.32.19443. [DOI] [PubMed] [Google Scholar]
  14. McClure S. J., Robinson P. J. Dynamin, endocytosis and intracellular signalling (review). Mol Membr Biol. 1996 Oct-Dec;13(4):189–215. doi: 10.3109/09687689609160598. [DOI] [PubMed] [Google Scholar]
  15. Moolenaar W. H., Kranenburg O., Postma F. R., Zondag G. C. Lysophosphatidic acid: G-protein signalling and cellular responses. Curr Opin Cell Biol. 1997 Apr;9(2):168–173. doi: 10.1016/s0955-0674(97)80059-2. [DOI] [PubMed] [Google Scholar]
  16. O'Farrell P. Z., Goodman H. M., O'Farrell P. H. High resolution two-dimensional electrophoresis of basic as well as acidic proteins. Cell. 1977 Dec;12(4):1133–1141. doi: 10.1016/0092-8674(77)90176-3. [DOI] [PubMed] [Google Scholar]
  17. Okabayashi Y., Sugimoto Y., Totty N. F., Hsuan J., Kido Y., Sakaguchi K., Gout I., Waterfield M. D., Kasuga M. Interaction of Shc with adaptor protein adaptins. J Biol Chem. 1996 Mar 1;271(9):5265–5269. doi: 10.1074/jbc.271.9.5265. [DOI] [PubMed] [Google Scholar]
  18. Robinson P. J., Sontag J. M., Liu J. P., Fykse E. M., Slaughter C., McMahon H., Südhof T. C. Dynamin GTPase regulated by protein kinase C phosphorylation in nerve terminals. Nature. 1993 Sep 9;365(6442):163–166. doi: 10.1038/365163a0. [DOI] [PubMed] [Google Scholar]
  19. Sternberg P. W., Alberola-Ila J. Conspiracy theory: RAS and RAF do not act alone. Cell. 1998 Nov 13;95(4):447–450. doi: 10.1016/s0092-8674(00)81612-8. [DOI] [PubMed] [Google Scholar]
  20. Sweitzer S. M., Hinshaw J. E. Dynamin undergoes a GTP-dependent conformational change causing vesiculation. Cell. 1998 Jun 12;93(6):1021–1029. doi: 10.1016/s0092-8674(00)81207-6. [DOI] [PubMed] [Google Scholar]
  21. Vieira A. V., Lamaze C., Schmid S. L. Control of EGF receptor signaling by clathrin-mediated endocytosis. Science. 1996 Dec 20;274(5295):2086–2089. doi: 10.1126/science.274.5295.2086. [DOI] [PubMed] [Google Scholar]
  22. Wan Y., Bence K., Hata A., Kurosaki T., Veillette A., Huang X. Y. Genetic evidence for a tyrosine kinase cascade preceding the mitogen-activated protein kinase cascade in vertebrate G protein signaling. J Biol Chem. 1997 Jul 4;272(27):17209–17215. doi: 10.1074/jbc.272.27.17209. [DOI] [PubMed] [Google Scholar]
  23. Wan Y., Kurosaki T., Huang X. Y. Tyrosine kinases in activation of the MAP kinase cascade by G-protein-coupled receptors. Nature. 1996 Apr 11;380(6574):541–544. doi: 10.1038/380541a0. [DOI] [PubMed] [Google Scholar]
  24. Wang Z., Moran M. F. Requirement for the adapter protein GRB2 in EGF receptor endocytosis. Science. 1996 Jun 28;272(5270):1935–1939. doi: 10.1126/science.272.5270.1935. [DOI] [PubMed] [Google Scholar]
  25. Ware M. F., Tice D. A., Parsons S. J., Lauffenburger D. A. Overexpression of cellular Src in fibroblasts enhances endocytic internalization of epidermal growth factor receptor. J Biol Chem. 1997 Nov 28;272(48):30185–30190. doi: 10.1074/jbc.272.48.30185. [DOI] [PubMed] [Google Scholar]
  26. Yoon S. Y., Koh W. S., Lee M. K., Park Y. M., Han M. Y. Dynamin II associates with Grb2 SH3 domain in Ras transformed NIH3T3 cells. Biochem Biophys Res Commun. 1997 May 29;234(3):539–543. doi: 10.1006/bbrc.1997.6676. [DOI] [PubMed] [Google Scholar]
  27. van Corven E. J., Hordijk P. L., Medema R. H., Bos J. L., Moolenaar W. H. Pertussis toxin-sensitive activation of p21ras by G protein-coupled receptor agonists in fibroblasts. Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1257–1261. doi: 10.1073/pnas.90.4.1257. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES