期刊
ONCOGENE
卷 19, 期 30, 页码 3445-3448出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1203688
关键词
MEN 2; RET-proto-oncogene; additional cysteine 634; ligand independent dimerization
Multiple endocrine neoplasia type 2A (MEN 2A) is a dominantly inherited canter syndrome, which involves the triad of MTC, pheochromocytoma, and hypcrparathyridism, Missense mutations in one of sis 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.
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