RalGDS functions in Ras- and cAMP-mediated growth stimulation

Marsha J. Miller, Sally Prigent, Erik Kupperman, Lise Rioux, Sang Ho Park, James R. Feramisco, Michael A. White, J. Lynn Rutkowski, Judy L. Meinkoth

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Thyroid-stimulating hormone stimulates proliferation through both the cAMP-dependent protein kinase and Ras but not through Raf-1 and mitogen- activated and extracellular signal-related kinase kinase. We now report that thyroid-stimulating hormone represses mitogen-activated protein kinase activity and that microinjection of an effector domain mutant Ha-Ras protein, Ras(12V,37G), defective in Raf-1 binding and mitogen-activated protein kinase activation, stimulates DNA synthesis in quiescent and thyroid-stimulating hormone-treated thyrocytes. A yeast two-hybrid screen identified RalGDS as a Ras(12V,37G) binding protein and therefore a potential effector of Ras in these cells. Associations between Ras and RalGDS were observed in extracts prepared from thyroid cells. Microinjection of a mutant RalA(28N) protein thought to sequester RalGDS family members reduced DNA synthesis stimulated by Ras as well as cAMP-mediated DNA synthesis in two cell lines which respond to cAMP with mitogenesis. These results support the idea that RalGDS may be an effector of Ras in cAMP-mediated growth stimulation.

Original languageEnglish (US)
Pages (from-to)5600-5605
Number of pages6
JournalJournal of Biological Chemistry
Volume272
Issue number9
DOIs
StatePublished - Feb 28 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Miller, M. J., Prigent, S., Kupperman, E., Rioux, L., Park, S. H., Feramisco, J. R., White, M. A., Rutkowski, J. L., & Meinkoth, J. L. (1997). RalGDS functions in Ras- and cAMP-mediated growth stimulation. Journal of Biological Chemistry, 272(9), 5600-5605. https://doi.org/10.1074/jbc.272.9.5600