Abstract
The RET proto-oncogene has been implicated in the causation of papillary thyroid carcinoma, multiple endocrine neoplasia types 2A (MEN 2A) and 2B (MEN 2B), and Hirschsprung's disease. The mutations in these syndromes can be categorized into activating or inactivating mutations. Activating mutations of a cysteine-rich extracellular region cause enhanced dimerization of the RET tyrosine kinase receptor and autophosphorylation, and are causative for MEN 2A and familial medullary thyroid carcinoma (FMTC). An activating mutation of the tyrosine kinase domain causes increased autophosphorylation but does not affect the state of dimerization. A variety of inactivating mutations of the RET proto-oncogene, which result in defective protein formation, are causative for Hirschsprung's disease.
MeSH terms
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Amino Acid Sequence
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Base Sequence
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Carcinoma / etiology
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Carcinoma / genetics
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Cysteine / metabolism
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Drosophila Proteins*
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Gene Expression / genetics
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Gene Expression / physiology*
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Hirschsprung Disease / etiology
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Hirschsprung Disease / genetics
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Humans
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Male
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Molecular Sequence Data
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Multiple Endocrine Neoplasia Type 2a / etiology
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Multiple Endocrine Neoplasia Type 2a / genetics*
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Multiple Endocrine Neoplasia Type 2b / etiology
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Multiple Endocrine Neoplasia Type 2b / genetics*
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Phosphorylation
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Point Mutation / genetics*
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Protein-Tyrosine Kinases / genetics*
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Proto-Oncogene Mas
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins c-ret
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Receptor Protein-Tyrosine Kinases / genetics*
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Thyroid Neoplasms / genetics
Substances
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Drosophila Proteins
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MAS1 protein, human
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Proto-Oncogene Mas
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Proto-Oncogene Proteins
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Protein-Tyrosine Kinases
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Proto-Oncogene Proteins c-ret
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Receptor Protein-Tyrosine Kinases
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Ret protein, Drosophila
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Cysteine