RAF kinase dimerization: implications for drug discovery and clinical outcomes

Analyses of the oncogenic BRAFD594G variant reveal a kinase-independent function of BRAF in activating MAPK signaling

(2020) Nicholas J. Cope et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Design and Synthesis of Type-IV Inhibitors of BRAF Kinase That Block Dimerization and Overcome Paradoxical MEK/ERK Activation

(2019) Chad M. Beneker et al.   JOURNAL OF MEDICINAL CHEMISTRY

Development of Allosteric BRAF Peptide Inhibitors Targeting the Dimer Interface of BRAF

(2019) Amber Y. Gunderwala et al.   ACS Chemical Biology

ARAF recurrent mutation causes central conducting lymphatic anomaly treatable with a MEK inhibitor

(2019) Dong Li et al.   NATURE MEDICINE

Combining the Allosteric Inhibitor Asciminib with Ponatinib Suppresses Emergence of and Restores Efficacy against Highly Resistant BCR-ABL1 Mutants

(2019) Christopher A. Eide et al.   CANCER CELL

Identification and characterization of a BRAF fusion oncoprotein with retained autoinhibitory domains

(2019) Florian Weinberg et al.   ONCOGENE

Cryo-EM structure of a dimeric B-Raf:14-3-3 complex reveals asymmetry in the active sites of B-Raf kinases

(2019) Yasushi Kondo et al.   SCIENCE

Architecture of autoinhibited and active BRAF–MEK1–14-3-3 complexes

(2019) Eunyoung Park et al.   NATURE

Genetic Heterogeneity of BRAF Fusion Kinases in Melanoma Affects Drug Responses

(2019) Thomas Botton et al.   Cell Reports

Distinct Binding Preferences between Ras and Raf Family Members and the Impact on Oncogenic Ras Signaling

(2019) Elizabeth M. Terrell et al.   MOLECULAR CELL

Current Insights of BRAF Inhibitors in Cancer

(2018) Bogos Agianian et al.   JOURNAL OF MEDICINAL CHEMISTRY

MEK drives BRAF activation through allosteric control of KSR proteins

(2018) Hugo Lavoie et al.   NATURE

A treatment strategy for KRAS-driven tumors

(2018) Trang T. Mai et al.   NATURE MEDICINE

BRAF inhibition upregulates a variety of receptor tyrosine kinases and their downstream effector Gab2 in colorectal cancer cell lines

(2018) Ricarda Herr et al.   ONCOGENE

Classifying BRAF alterations in cancer: new rational therapeutic strategies for actionable mutations

(2018) Matthew Dankner et al.   ONCOGENE

The dimer-dependent catalytic activity of RAF family kinases is revealed through characterizing their oncogenic mutants

(2018) Jimin Yuan et al.   ONCOGENE

Ras-Mediated Activation of the Raf Family Kinases

(2018) Elizabeth M. Terrell et al.   Cold Spring Harbor Perspectives in Medicine

Dissecting RAF Inhibitor Resistance by Structure-based Modeling Reveals Ways to Overcome Oncogenic RAS Signaling

(2018) Oleksii S. Rukhlenko et al.   Cell Systems

Allosteric activation of RAF in the MAPK signaling pathway

(2018) Chung-Jung Tsai et al.   CURRENT OPINION IN STRUCTURAL BIOLOGY

Proceedings of the fifth international RASopathies symposium: When development and cancer intersect

(2018) Katherine A. Rauen et al.   AMERICAN JOURNAL OF MEDICAL GENETICS PART A

RAF inhibitor PLX8394 selectively disrupts BRAF dimers and RAS-independent BRAF-mutant-driven signaling

(2018) Zhan Yao et al.   NATURE MEDICINE

A compendium of ERK targets

(2017) Evrim B. Ünal et al.   FEBS LETTERS

Phosphorylation of the C-Raf N Region Promotes Raf Dimerization

(2017) Maho Takahashi et al.   MOLECULAR AND CELLULAR BIOLOGY

Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS

(2017) Zhan Yao et al.   NATURE

CRAF gene fusions in pediatric low-grade gliomas define a distinct drug response based on dimerization profiles

(2017) P Jain et al.   ONCOGENE

BRAF inhibition in hairy cell leukemia with low-dose vemurafenib

(2016) S. Dietrich et al.   BLOOD

Activation Mechanism of Oncogenic Deletion Mutations in BRAF, EGFR, and HER2

(2016) Scott A. Foster et al.   CANCER CELL

An Integrated Model of RAF Inhibitor Action Predicts Inhibitor Activity against Oncogenic BRAF Signaling

(2016) Zoi Karoulia et al.   CANCER CELL

Regulation of BRAF protein stability by a negative feedback loop involving the MEK–ERK pathway but not the FBXW7 tumour suppressor

(2016) Maria Aguilar Hernandez et al.   CELLULAR SIGNALLING

Oncogenic BRAF Deletions That Function as Homodimers and Are Sensitive to Inhibition by RAF Dimer Inhibitor LY3009120

(2016) S.-H. Chen et al.   Cancer Discovery

Phospho-proteomic analyses of B-Raf protein complexes reveal new regulatory principles

(2016) Anja E. Eisenhardt et al.   Oncotarget

Phosphorylation of RAF Kinase Dimers Drives Conformational Changes that Facilitate Transactivation

(2015) Pablo G. Jambrina et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers

(2015) Sheng-Bin Peng et al.   CANCER CELL

BRAF Mutants Evade ERK-Dependent Feedback by Different Mechanisms that Determine Their Sensitivity to Pharmacologic Inhibition

(2015) Zhan Yao et al.   CANCER CELL

Activation loop phosphorylation regulates B-Raf in vivo and transformation by B-Raf mutants

(2015) M. Ko hler et al.   EMBO JOURNAL

The distribution ofBRAFgene fusions in solid tumors and response to targeted therapy

(2015) Jeffrey S. Ross et al.   INTERNATIONAL JOURNAL OF CANCER

The Effect of a Widespread Cancer-Causing Mutation on the Inactive to Active Dynamics of the B-Raf Kinase

(2015) Kristen A. Marino et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Cooperation of BRAFF595L and mutant HRAS in histiocytic sarcoma provides new insights into oncogenic BRAF signaling

(2015) M Kordes et al.   LEUKEMIA

Regulation of RAF protein kinases in ERK signalling

(2015) Hugo Lavoie et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Diverse and Targetable Kinase Alterations Drive Histiocytic Neoplasms

(2015) E. L. Diamond et al.   Cancer Discovery

Drug Resistance Resulting from Kinase Dimerization Is Rationalized by Thermodynamic Factors Describing Allosteric Inhibitor Effects

(2015) Boris N. Kholodenko   Cell Reports

Molecular mechanisms of asymmetric RAF dimer activation

(2014) Pablo G. Jambrina et al.   BIOCHEMICAL SOCIETY TRANSACTIONS

Kinase Regulation by Hydrophobic Spine Assembly in Cancer

(2014) Jiancheng Hu et al.   MOLECULAR AND CELLULAR BIOLOGY

Crystal structure of a BRAF kinase domain monomer explains basis for allosteric regulation

(2014) Neroshan Thevakumaran et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Mapping the molecular determinants of BRAF oncogene dependence in human lung cancer

(2014) L. Lin et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Dimerization of the kinase ARAF promotes MAPK pathway activation and cell migration

(2014) J. Mooz et al.   Science Signaling

Allosteric Activation of Functionally Asymmetric RAF Kinase Dimers

(2013) Jiancheng Hu et al.   CELL

Effects of Raf Dimerization and Its Inhibition on Normal and Disease-Associated Raf Signaling

(2013) Alyson K. Freeman et al.   MOLECULAR CELL

Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma

(2013) David T W Jones et al.   NATURE GENETICS

Paradoxical activation and RAF inhibitor resistance of BRAF protein kinase fusions characterizing pediatric astrocytomas

(2013) A. J. Sievert et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Distinct requirement for an intact dimer interface in wild-type, V600E and kinase-dead B-Raf signalling

(2012) Michael Röring et al.   EMBO JOURNAL

Increased BRAF Heterodimerization Is the Common Pathogenic Mechanism for Noonan Syndrome-Associated RAF1 Mutants

(2012) X. Wu et al.   MOLECULAR AND CELLULAR BIOLOGY

Mechanisms of acquired resistance to ERK1/2 pathway inhibitors

(2012) A S Little et al.   ONCOGENE

Single Substitution within the RKTR Motif Impairs Kinase Activity but Promotes Dimerization of RAF Kinase

(2011) Angela Baljuls et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)

(2011) Poulikos I. Poulikakos et al.   NATURE

Mutation that blocks ATP binding creates a pseudokinase stabilizing the scaffolding function of kinase suppressor of Ras, CRAF and BRAF

(2011) J. Hu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Kinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression through CRAF

(2010) Sonja J. Heidorn et al.   CELL

RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF

(2010) Poulikos I. Poulikakos et al.   NATURE

RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth

(2010) Georgia Hatzivassiliou et al.   NATURE

Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma

(2010) Gideon Bollag et al.   NATURE

A dimerization-dependent mechanism drives RAF catalytic activation

(2009) Thanashan Rajakulendran et al.   NATURE

Characterization of Ser338Phosphorylation for Raf-1 Activation

(2008) Mengwei Zang et al.   JOURNAL OF BIOLOGICAL CHEMISTRY