Activation mechanisms of clinically distinct B-Raf V600Eand V600K mutants  

作　　者：Mingzhen Zhang Ryan Maloney Yonglan Liu Hyunbum Jang Ruth Nussinov 

机构地区：[1]Computational Structural Biology Section,Frederick National Laboratory for Cancer Research,Frederick,MD,U.S.A. [2]Cancer Innovation Laboratory,National Cancer Institute,Frederick,MD,U.S.A. [3]Department of Human Molecular Genetics and Biochemistry,Sackler School of Medicine,Tel Aviv University,Tel Aviv,Israel

出　　处：《Cancer Communications》2023年第3期405-408,共4页癌症通讯（英文）

基　　金：the National Cancer Institute,National Institutes of Health,under contract HHSN261201500003I.

摘　　要：Dear Editor,B-Raf,the main effector of Ras in the mitogen-activated protein kinase(MAPK)pathway,is among the most highly mutated kinases in human cancer[1].About 40%-60%of melanoma patients harbor B-Raf mutations,of which∼90%involve V600E and V600K.B-RafV600E is more frequent(60%-80%)than B-RafV600K(10%-30%).Substitution of a Val codon by Glu requires a single nucleotide change,whereas Val to Lys requires two[2].This is in line with melanoma patients harboring the V600K mutation,who usually suffer from higher sun exposure that may induce increased DNA damage[3].Since both mutations occur at the same position of the kinase domain and are mutated to charged residues,it was believed that the B-Raf V600E and V600K mutantswould share a similar behavior,and in clinical trials,patients with V600E and V600K mutations have been recruited into the same cohort.

关 键 词：V600E V600 MELANOMA 

分 类 号：R730[医药卫生—肿瘤]