Hyperactive Ras in developmental disorders and cancer.
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.
Schubbert
Suzanne
S
Department of Pediatrics, University of California, 513 Parnassus Avenue, Room HSE-302, San Francisco, California 94143, USA.
Shannon
Kevin
K
Bollag
Gideon
G
D002675:Child, Preschool; D002658:Developmental Disabilities / Q000235:genetics*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics; D005786:Gene Expression Regulation; D011905:Genes, ras; D018095:Germ-Line Mutation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D020935:MAP Kinase Signaling System; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics; D008958:Models, Molecular; D009369:Neoplasms / Q000235:genetics*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics; D015398:Signal Transduction
D047908:Intracellular Signaling Peptides and Proteins; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases