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Biological effects of the dual phenotypic Janus mutation of ret cosegregating with both multiple endocrine neoplasia type 2 and Hirschsprung's disease.
Mol Endocrinol. 2004 Apr; 18(4):1004-17.ME

Abstract

Gain-of-function mutations of ret receptor tyrosine kinase, the signaling receptor for glial cell line-derived neurotrophic factor, cause sporadic thyroid and adrenal malignancies as well as endocrine cancer syndromes, such as multiple endocrine neoplasia types 2A and 2B (MEN 2A and MEN 2B) and familial medullary thyroid carcinoma. Loss-of-function mutations of ret cause Hirschsprung's disease (HSCR) or colonic aganglionosis. In 20-30% of families with a mutation at residues 609, 611, 618, or 620 of RET, MEN 2A and familial medullary thyroid carcinoma cosegregate with HSCR. These mutations constitutively activate RET due to aberrant disulfide homodimerization and diminish the level of RET at the plasma membrane. It is not known how these mutations simultaneously lead to both gain- and loss-of-function RET-associated diseases. We provide an explanation for the dual phenotypic Janus mutation at Cys620 of RET. In Madin-Darby canine kidney (MDCK) cells, the Janus mutation impairs the glial cell line-derived neurotrophic factor-induced effects of RET on cell migration, differentiation, and survival but simultaneously promotes rapid cell proliferation.

Authors+Show Affiliations

Developmental Biology, Institute of Biomedicine, Biomedicum Helsinki, P.O. Box 63, University of Helsinki, Helsinki, Finland FIN-00014.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14715928

Citation

Arighi, Elena, et al. "Biological Effects of the Dual Phenotypic Janus Mutation of Ret Cosegregating With Both Multiple Endocrine Neoplasia Type 2 and Hirschsprung's Disease." Molecular Endocrinology (Baltimore, Md.), vol. 18, no. 4, 2004, pp. 1004-17.
Arighi E, Popsueva A, Degl'Innocenti D, et al. Biological effects of the dual phenotypic Janus mutation of ret cosegregating with both multiple endocrine neoplasia type 2 and Hirschsprung's disease. Mol Endocrinol. 2004;18(4):1004-17.
Arighi, E., Popsueva, A., Degl'Innocenti, D., Borrello, M. G., Carniti, C., Perälä, N. M., Pierotti, M. A., & Sariola, H. (2004). Biological effects of the dual phenotypic Janus mutation of ret cosegregating with both multiple endocrine neoplasia type 2 and Hirschsprung's disease. Molecular Endocrinology (Baltimore, Md.), 18(4), 1004-17.
Arighi E, et al. Biological Effects of the Dual Phenotypic Janus Mutation of Ret Cosegregating With Both Multiple Endocrine Neoplasia Type 2 and Hirschsprung's Disease. Mol Endocrinol. 2004;18(4):1004-17. PubMed PMID: 14715928.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Biological effects of the dual phenotypic Janus mutation of ret cosegregating with both multiple endocrine neoplasia type 2 and Hirschsprung's disease. AU - Arighi,Elena, AU - Popsueva,Anna, AU - Degl'Innocenti,Debora, AU - Borrello,Maria Grazia, AU - Carniti,Cristiana, AU - Perälä,Nina M, AU - Pierotti,Marco A, AU - Sariola,Hannu, Y1 - 2004/01/08/ PY - 2004/1/13/pubmed PY - 2004/12/16/medline PY - 2004/1/13/entrez SP - 1004 EP - 17 JF - Molecular endocrinology (Baltimore, Md.) JO - Mol Endocrinol VL - 18 IS - 4 N2 - Gain-of-function mutations of ret receptor tyrosine kinase, the signaling receptor for glial cell line-derived neurotrophic factor, cause sporadic thyroid and adrenal malignancies as well as endocrine cancer syndromes, such as multiple endocrine neoplasia types 2A and 2B (MEN 2A and MEN 2B) and familial medullary thyroid carcinoma. Loss-of-function mutations of ret cause Hirschsprung's disease (HSCR) or colonic aganglionosis. In 20-30% of families with a mutation at residues 609, 611, 618, or 620 of RET, MEN 2A and familial medullary thyroid carcinoma cosegregate with HSCR. These mutations constitutively activate RET due to aberrant disulfide homodimerization and diminish the level of RET at the plasma membrane. It is not known how these mutations simultaneously lead to both gain- and loss-of-function RET-associated diseases. We provide an explanation for the dual phenotypic Janus mutation at Cys620 of RET. In Madin-Darby canine kidney (MDCK) cells, the Janus mutation impairs the glial cell line-derived neurotrophic factor-induced effects of RET on cell migration, differentiation, and survival but simultaneously promotes rapid cell proliferation. SN - 0888-8809 UR - https://www.unboundmedicine.com/medline/citation/14715928/Biological_effects_of_the_dual_phenotypic_Janus_mutation_of_ret_cosegregating_with_both_multiple_endocrine_neoplasia_type_2_and_Hirschsprung's_disease_ L2 - https://academic.oup.com/mend/article-lookup/doi/10.1210/me.2003-0173 DB - PRIME DP - Unbound Medicine ER -