RET activation by germline MEN2A and MEN2B mutations.

摘要: The RET proto-oncogene encodes a receptor tyrosine kinase (TK). It has been shown that distinct germline mutations in the are associated with dominantly inherited cancer syndromes multiple endocrine neoplasia type 2A and 2B (MEN MEN 2B) familial medullary thyroid carcinoma (FMTC) as well Hirschsprung disease (HSCR), congenital disorder characterised by absent enteric innervation. In this study, we have transfected NIH3T3 PC12 phaeochromocytoma cells MEN2A (Cys634-> Arg) MEN2B (Met918-> Thr) constructs. Both caused transformation of differentiation cells. Ret (MEN2A) (MEN2B) proteins were constitutively phosphorylated on tyrosine, their vitro activity was significantly higher than wild protein. MTC cell line TT carries CYs634-> Trp mutation, immunoelectronmicroscopy is clustered surface manner reminiscent ligand-induced aggregation receptors. activated, RET/PTC oncogene, somatic rearrangements which link TK domain to constitutive dimerization interface papillary carcinomas. We compared biological biochemical domains context RET/PTC. results show mutation increases enzymatic suggesting may be still necessary for express its full activity.