Functional analysis of mutations within the kinase activation segment of B-Raf in human colorectal tumors.
作者： Yohko Hikiba , Tsuneo Ikenoue , Hideaki Ijichi , Jun Aragaki , Keisuke Tateishi
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摘要: Mutations in the B-Raf gene have been reported a number of human cancers, including colorectal carcinoma. More than 80% mutations were V599E. Although other reported, their functional consequences unclear. Here, we examined effect colon tumor-associated within kinase activation segment, V599E, on extracellular signal-regulated (Erk) and nuclear factor kappaB (NFkappaB) signaling, transformation NIH3T3 fibroblasts. Among six examined, only V599E K600E greatly increased Erk NFkappaB cells. The F594L mutation moderately elevated signaling transformation, but did not significantly increase signaling. basal activity T598I mutant was comparable with that wild-type, its oncogenic Ras-induced decreased to 60% wild-type activity. D593V G595R mutants showed severely reduced affected neither nor transforming These results suggest segment tumors do necessarily contribute carcinogenesis by increasing activities.
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