Biochemical Society Transactions, Volume (46), No (6), Year (2018-12) , Pages (1393-1406)

Title : ( Structural snapshots of RAF kinase interactions )

Authors: Soheila Rezaei Adarian , Marcel Buchholzer , Mohammad Akbarzadeh , Saeideh Nakhaeirad , .Radovan Dvorsky , Mohammad Reza Ahmadian ,

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Abstract

RAF (rapidly accelerated fibrosarcoma) Ser/Thr kinases (ARAF, BRAF, and CRAF) link the RAS (rat sarcoma) protein family with the MAPK (mitogen-activated protein kinase) pathway and control cell growth, differentiation, development, aging, and tumorigenesis. Their activity is specifically modulated by protein-protein interactions, post-translational modifications, and conformational changes in specific spatiotemporal patterns via various upstream regulators, including the kinases, phosphatase, GTPases, and scaffold and modulator proteins. Dephosphorylation of Ser-259 (CRAF numbering) and dissociation of 14-3-3 release the RAF regulatory domains RAS-binding domain and cysteine-rich domain for interaction with RAS-GTP and membrane lipids. This, in turn, results in RAF phosphorylation at Ser-621 and 14-3-3 reassociation, followed by its dimerization and ultimately substrate binding and phosphorylation. This review focuses on structural understanding of how distinct binding partners trigger a cascade of molecular events that induces RAF kinase activation.

Keywords

, 14, 3, 3 proteins; RAF kinases; RAS; RAS, binding domain; cysteine, rich domains; membrane lipids
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@article{paperid:1077927,
author = {Soheila Rezaei Adarian and Marcel Buchholzer and محمد اکبرزاده and Nakhaeirad, Saeideh and Radovan Dvorsky and محمد رضا احمدیان},
title = {Structural snapshots of RAF kinase interactions},
journal = {Biochemical Society Transactions},
year = {2018},
volume = {46},
number = {6},
month = {December},
issn = {0300-5127},
pages = {1393--1406},
numpages = {13},
keywords = {14-3-3 proteins; RAF kinases; RAS; RAS-binding domain; cysteine-rich domains; membrane lipids},
}

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%0 Journal Article
%T Structural snapshots of RAF kinase interactions
%A Soheila Rezaei Adarian
%A Marcel Buchholzer
%A محمد اکبرزاده
%A Nakhaeirad, Saeideh
%A Radovan Dvorsky
%A محمد رضا احمدیان
%J Biochemical Society Transactions
%@ 0300-5127
%D 2018

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