Hyperactive Ras in developmental disorders and cancer

Nat Rev Cancer. 2007 Apr;7(4):295-308. doi: 10.1038/nrc2109.


Ras genes are the most common targets for somatic gain-of-function mutations in human cancer. Recently, germline mutations that affect components of the Ras-Raf-mitogen-activated and extracellular-signal regulated kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway were shown to cause several developmental disorders, including Noonan, Costello and cardio-facio-cutaneous syndromes. Many of these mutant alleles encode proteins with aberrant biochemical and functional properties. Here we will discuss the implications of germline mutations in the Ras-Raf-MEK-ERK pathway for understanding normal developmental processes and cancer pathogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Child, Preschool
  • Developmental Disabilities / genetics*
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Gene Expression Regulation
  • Genes, ras*
  • Germ-Line Mutation*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • MAP Kinase Signaling System
  • Mitogen-Activated Protein Kinase Kinases
  • Mitogen-Activated Protein Kinases / genetics
  • Models, Molecular
  • Neoplasms / genetics*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatases / genetics
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins c-raf / genetics
  • Signal Transduction


  • Intracellular Signaling Peptides and Proteins
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins c-raf
  • Extracellular Signal-Regulated MAP Kinases
  • Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase Kinases
  • PTPN11 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatases