Abstract
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
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Review
MeSH terms
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Child, Preschool
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Developmental Disabilities / genetics*
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Extracellular Signal-Regulated MAP Kinases / genetics
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Gene Expression Regulation
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Genes, ras*
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Germ-Line Mutation*
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Humans
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Intracellular Signaling Peptides and Proteins / genetics
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MAP Kinase Signaling System
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Mitogen-Activated Protein Kinase Kinases
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Mitogen-Activated Protein Kinases / genetics
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Models, Molecular
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Neoplasms / genetics*
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatases / genetics
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Proto-Oncogene Proteins B-raf / genetics
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Proto-Oncogene Proteins c-raf / genetics
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Signal Transduction
Substances
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Intracellular Signaling Peptides and Proteins
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Proto-Oncogene Proteins B-raf
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Proto-Oncogene Proteins c-raf
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Extracellular Signal-Regulated MAP Kinases
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Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinase Kinases
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PTPN11 protein, human
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatases