R-Ras is regulated by activators and effectors distinct from those that control Ras function

Shayne Y. Huff, Lawrence Quilliam, Adrienne D. Cox, Channing J. Der

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Like Ras, constitutively activated mutants of the Ras-related protein R-Ras cause tumorigenic transformation of NIH3T3 cells. However, since R-Ras causes transformed phenotype distinct from that induced by Ras, it is likely that R-Ras controls signaling pathways and cellular processes distinct from those regulated by Ras. To address this possibility, we determined if R-Ras is regulated by activators and effectors distinct from those that regulate Ras function. We observed that Ras guanine nucleotide exchange factors failed to activate R-Ras in vivo, indicating that R-Ras is activated by distinct GEFs. Consistent with this, mutants of R-Ras with mutations analogous to the Ras(15A)/(17N) dominant negative proteins did not antagonize Ras GEF function and lacked the growth inhibitory activity seen with these mutant Ras proteins. Thus, R-Ras, but not Ras, is dispensable for the viability of NIH3T3 cells. Finally, whereas constitutively activated Ras can overcome the growth inhibitory action of the Ras(17N) dominant negative protein via Raf-dependent and -independent activities, transforming mutants of R-Ras failed to do so. This inability was consistent with our observation that Ras-, but not R-Ras-transformed, NIH3T3 cells possessed constitutively upregulated Raf kinase activities. Thus, R-Ras and Ras are regulators of distinct signaling pathways and cellular processes.

Original languageEnglish
Pages (from-to)133-143
Number of pages11
JournalOncogene
Volume14
Issue number2
StatePublished - 1997

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ras Guanine Nucleotide Exchange Factors
ras Proteins
raf Kinases
Neoplastic Cell Transformation
Mutant Proteins
Growth
Cell Survival
Proteins
Phenotype
Mutation

Keywords

  • Dominant negative mutants
  • GDP
  • GTP regulation
  • Raf kinases

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

R-Ras is regulated by activators and effectors distinct from those that control Ras function. / Huff, Shayne Y.; Quilliam, Lawrence; Cox, Adrienne D.; Der, Channing J.

In: Oncogene, Vol. 14, No. 2, 1997, p. 133-143.

Research output: Contribution to journalArticle

Huff, Shayne Y. ; Quilliam, Lawrence ; Cox, Adrienne D. ; Der, Channing J. / R-Ras is regulated by activators and effectors distinct from those that control Ras function. In: Oncogene. 1997 ; Vol. 14, No. 2. pp. 133-143.
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