Ras proteins in the control of the cell cycle and cell differentiation

Cell Mol Life Sci. 2000 Oct;57(11):1613-36. doi: 10.1007/pl00000645.


The Ras family of small GTPases includes three closely related proteins: H-, K-, and N-Ras. Ras proteins are involved in the transduction of signals elicited by activated surface receptors, acting as key components by relaying signals downstream through diverse pathways. Mutant, constitutively activated forms of Ras proteins are frequently found in cancer. While constitutive Ras activation induces oncogenic-like transformation in immortalized fibroblasts, it causes growth arrest in primary vertebrate cells. Induction of p53 and cyclin-dependent kinase inhibitors such as p15INK4b, p16INK4a, p19ARF, and p21WAF1 accounts for this response. Interestingly, while ras has usually been regarded as a transforming oncogene, the analysis of Ras function in most of the cellular systems studied so far indicates that the promotion of differentiation is the most prominent effect of Ras. While in some cell types, particularly muscle, Ras inhibits differentiation, in others such as neuronal, adipocytic, or myeloid cells, Ras induces differentiation, in some cases accompanied by growth arrest. Several possible mechanisms for the pleiotropic effects' of Ras in animal cells are discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Cycle*
  • Cell Differentiation*
  • Cells / cytology*
  • Cells / enzymology
  • Cells / metabolism*
  • Cyclins / metabolism
  • Humans
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Signal Transduction
  • ras Proteins / chemistry
  • ras Proteins / genetics
  • ras Proteins / metabolism*
  • rho GTP-Binding Proteins / metabolism


  • Cyclins
  • Phosphatidylinositol 3-Kinases
  • Mitogen-Activated Protein Kinases
  • ras Proteins
  • rho GTP-Binding Proteins