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- Title
A novel type of mutation in the cysteine rich domain of the RET receptor causes ligand independent activation.
- Authors
Arlt, D H; Baur, B; Wagner, B; Höppner, W
- Abstract
Multiple endocrine neoplasia type 2A (MEN 2A) is a dominantly inherited cancer syndrome, which involves the triad of MTC, pheochromocytoma, and hyperparathyridism. Missense mutations in one of six cysteine codons in the extracellular cysteine-rich domain of the RET proto-oncogene predispose to this disease. These mutations cause ligand-independent constitutive activation of the tyrosine kinase receptor by the formation of disulfide-bonded homodimers. We examined a different type of mutation, which results in an additional cysteine in the cysteine rich domain. A duplication of 9 bp in the first case resulted in an insertion of three amino acids between codon 633 and 634. In the second case a 12 bp duplication in exon 11 results in four additional amino acids between codon 634 and 635. Here we demonstrate that an additional cysteine causes a ligand independent dimerization of the RET receptor in transfected NIH3T3 cells, which results in an activation of the intracellular tyrosine kinase. Oncogene (2000) 19, 3445–3448
- Subjects
CANCER; GENETIC mutation; ONCOGENES; PROTEIN-tyrosine kinases
- Publication
Oncogene, 2000, Vol 19, Issue 30, p3445
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1203688