Falcon deep research report for human BRAF
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Falcon synthesis supports BRAF as the RAF-family MAP3K that directly phosphorylates and activates MEK1/MEK2 in the ERK pathway.
"BRAF is a RAF-family kinase whose primary role in the ERK pathway is to act as a MAP kinase kinase kinase (MAP3K) that phosphorylates and activates MEK1/MEK2."
Gene Ontology annotation through association of InterPro records with GO terms
Gene Ontology annotation based on Enzyme Commission mapping
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Automatic assignment of GO terms using logical inference, based on on inter-ontology links
Automatic Gene Ontology annotation based on Rhea mapping
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Di-Ras, a distinct subgroup of ras family GTPases with unique biochemical properties.
Novel raf kinase protein-protein interactions found by an exhaustive yeast two-hybrid analysis.
Comprehensive proteomic analysis of interphase and mitotic 14-3-3-binding proteins.
Targeted proteomic analysis of 14-3-3 sigma, a p53 effector commonly silenced in cancer.
FGF-2 protects small cell lung cancer cells from apoptosis through a complex involving PKCepsilon, B-Raf and S6K2.
The amino-terminal B-Raf-specific region mediates calcium-dependent homo- and hetero-dimerization of Raf.
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The B-Raf-specific amino-terminal region is essential for calcium-dependent homo- and heterodimerization of BRAF at the plasma membrane; increased intracellular calcium is necessary for dimerization and sufficient for plasma membrane translocation
"this amino-terminal B-Raf-specific region is essential for homo-dimerization of B-Raf and hetero-dimerization of B-Raf and c-Raf at the plasma membrane, followed by phosphorylation of Thr118 in the amino-terminal B-Raf-specific region"
Glucocorticoids cause rapid dissociation of a T-cell-receptor-associated protein complex containing LCK and FYN.
Selective role for RGS12 as a Ras/Raf/MEK scaffold in nerve growth factor-mediated differentiation.
IQGAP1 modulates activation of B-Raf.
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IQGAP1 is a scaffold required for B-Raf activation by EGF; IQGAP1-null cells and cells expressing an IQGAP1 mutant unable to bind B-Raf fail to stimulate B-Raf activity in response to EGF; IQGAP1 binding directly enhances B-Raf kinase activity in vitro
"EGF is unable to stimulate B-Raf activity in IQGAP1-null cells and in cells transfected with an IQGAP1 mutant construct that is unable to bind B-Raf"
A novel tandem affinity purification strategy for the efficient isolation and characterisation of native protein complexes.
IQGAP1 integrates Ca2+/calmodulin and B-Raf signaling.
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IQGAP1 mediates crosstalk from Ca2+ and calmodulin signaling to B-Raf; Ca2+ promotes IQGAP1-B-Raf binding while Ca2+/calmodulin abrogates it, and chelating intracellular Ca2+ enhances EGF-stimulated B-Raf activity in an IQGAP1-dependent manner
"Ca 2+ promotes the direct binding of IQGAP1 to B-Raf. This interaction is inhibited by calmodulin in a Ca 2+ -regulated manner"
Identification of novel in vivo phosphorylation sites of the human proapoptotic protein BAD: pore-forming activity of BAD is regulated by phosphorylation.
Diacylglycerol kinase eta augments C-Raf activity and B-Raf/C-Raf heterodimerization.
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Diacylglycerol kinase eta (DGKeta) functions as a scaffold/adaptor that promotes B-Raf/C-Raf heterodimerization in a kinase-activity-independent manner; DGKeta knockdown impairs EGF-stimulated Ras/B-Raf/C-Raf/MEK/ERK signaling
"DGKeta1 could activate the Ras/B-Raf/C-Raf/MEK/ERK pathway in a DGK activity-independent manner, suggesting that DGKeta serves as a scaffold/adaptor protein"
A dimerization-dependent mechanism drives RAF catalytic activation.
RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth.
Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF.
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Kinase-dead BRAF cooperates with oncogenic RAS to drive tumor progression through CRAF; RAF inhibitors that selectively inhibit BRAF paradoxically activate this kinase-dead BRAF/oncogenic RAS/CRAF signaling axis
"drugs that selectively inhibit BRAF activate RAS-dependent kinase-dead BRAF signaling through CRAF"
A Raf-induced allosteric transition of KSR stimulates phosphorylation of MEK.
ERK and PDE4 cooperate to induce RAF isoform switching in melanoma.
A novel requirement for Janus kinases as mediators of drug resistance induced by fibroblast growth factor-2 in human cancer cells.
Oncogenic Ras and B-Raf proteins positively regulate death receptor 5 expression through co-activation of ERK and JNK signaling.
Nilotinib and MEK inhibitors induce synthetic lethality through paradoxical activation of RAF in drug-resistant chronic myeloid leukemia.
Distinct requirement for an intact dimer interface in wild-type, V600E and kinase-dead B-Raf signalling.
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The kinase-domain dimer interface is pivotal for wild-type BRAF activity, whereas oncogenic BRAF(V600E) and BRAF(G469A) are resistant to dimer-interface mutations and display extended protomer contacts and increased homodimerization
"the B-Raf(V600E), B-Raf(insT) and B-Raf(G469A) oncoproteins are remarkably resistant to mutations in the DIF. However, compared with B-Raf(wt), B-Raf(V600E) displays extended protomer contacts, increased homodimerisation and incorporation into larger protein complexes"
Complete coding sequence of a human B-raf cDNA and detection of B-raf protein kinase with isozyme specific antibodies.
Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition.
Stimulation of the Na(+)-coupled glucose transporter SGLT1 by B-RAF.
Relief of profound feedback inhibition of mitogenic signaling by RAF inhibitors attenuates their activity in BRAFV600E melanomas.
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RAF inhibitors relieve profound ERK-dependent negative feedback in BRAF(V600E) melanomas, paradoxically reactivating upstream RAS signaling; this feedback relief attenuates the antiproliferative effect of RAF inhibitors
"RAF inhibitors effectively inhibit ERK signaling only in tumors with mutant BRAF"
RAF inhibitors activate the MAPK pathway by relieving inhibitory autophosphorylation.
Mechanism of MEK inhibition determines efficacy in mutant KRAS- versus BRAF-driven cancers.
Protein interaction network of the mammalian Hippo pathway reveals mechanisms of kinase-phosphatase interactions.
Integrated RAS signaling defined by parallel NMR detection of effectors and regulators.
Disruption of CRAF-mediated MEK activation is required for effective MEK inhibition in KRAS mutant tumors.
Structure of the BRAF-MEK complex reveals a kinase activity independent role for BRAF in MAPK signaling.
Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network.
Crystal structure of a BRAF kinase domain monomer explains basis for allosteric regulation.
Tunable-combinatorial mechanisms of acquired resistance limit the efficacy of BRAF/MEK cotargeting but result in melanoma drug addiction.
The RAS-Binding Domain of Human BRAF Protein Serine/Threonine Kinase Exhibits Allosteric Conformational Changes upon Binding HRAS.
RAF inhibitors that evade paradoxical MAPK pathway activation.
A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance drug binding.
Architecture of the human interactome defines protein communities and disease networks.
MEK drives BRAF activation through allosteric control of KSR proteins.
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MEK binding to the KSR1 kinase domain asymmetrically drives BRAF-KSR1 heterodimerization, stimulating BRAF catalytic activity toward free MEK molecules
"MEK binding to the kinase domain of KSR1 asymmetrically drives BRAF-KSR1 heterodimerization, resulting in the concomitant stimulation of BRAF catalytic activity towards free MEK molecules"
Interrogating the protein interactomes of RAS isoforms identifies PIP5K1A as a KRAS-specific vulnerability.
A YWHAZ Variant Associated With Cardiofaciocutaneous Syndrome Activates the RAF-ERK Pathway.
Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D).
Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity.
Systematic discovery of mutation-directed neo-protein-protein interactions in cancer.
A Proteomic Approach Identifies Isoform-Specific and Nucleotide-Dependent RAS Interactions.
HERC2 deficiency activates C-RAF/MKK3/p38 signalling pathway altering the cellular response to oxidative stress.
A central chaperone-like role for 14-3-3 proteins in human cells.
Interactome dynamics of RAF1-BRAF kinase monomers and dimers.
Multimodal cell maps as a foundation for structural and functional genomics.
Endothelial apoptosis in Braf-deficient mice.
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Braf-/- mice die of vascular defects during mid-gestation; embryos show increased endothelial precursor cells, dramatically enlarged blood vessels, and apoptotic death of differentiated endothelial cells, establishing BRAF as critical for vascular system formation
B-RAF dissociates from S110/S120 p-SPRY2
SPRY2 is serine phosphorylated in response to MAPK activation
"Activator" RAF:YWHAB dimer binds RAS:GTP
YWHAB dimer dissociates from dephosphorylated RAF
PP2A dephosphorylates inactive RAFs
RAS:GTP:'activator' RAF homo/heterodimerizes with other RAF monomers
MAP2Ks and MAPKs bind to the activated RAF complex
MAP2Ks phosphorylate MAPKs
RAF phosphorylates MAP2K dimer
Dissociation of RAS:RAF complex
MAP2Ks and MAPKs are phosphorylated at the endosome membrane
WDR83:LAMTOR2:LAMTOR3 binds MAPK components
PAQR3 binds inactive RAFs
Activated MAPKs phosphorylate BRAF
PEBP1 binds activated RAF1
PP2A dephosphorylates RAF1
PP5 dephosphorylates RAF1 S338
RAS mutants bind inactive RAF
Activated MAP2Ks phosphorylate MAPKs downstream of high kinase activity BRAF mutants
High kinase activity BRAF complexes phosphorylate MAP2Ks
High kinase activity BRAF mutants bind MAP2Ks and MAPKs
RAS:GTP:moderate kinase activity p-RAF complexes bind MAP2Ks and MAPKs
Moderate kinase activity BRAF mutants bind RAS:GTP
RAF is phosphorylated downstream of moderate kinase activity BRAF mutants
Activated MAP2Ks phosphorylate MAPKs downstream of inactive BRAF mutants
RAS:GTP:moderate kinase activity p-RAF complexes phosphorylate MAP2Ks
Activated MAP2Ks phosphorylate MAPKs downstream of moderate kinase activity BRAF mutants
Activated MAP2Ks phosphorylate MAPKs downstream of oncogenic RAS
RAF is phosphorylated downstream of oncogenic RAS
Mutant RAS:p-RAF complexes bind MAP2Ks and MAPKs
Mutant RAS:p-RAF complexes phosphorylate MAP2Ks
Dimerization of BRAF V600E splice variants contributes to BRAF inhibitor resistance
Inactive BRAF mutants bind mutant RAS:GTP
Inhibitors bind and inhibit highly active BRAF mutants
RAF is paradoxically phosphorylated downstream of kinase-inactive RAF
RAS:GTP:p-RAF complexes paradoxically bind MAP2Ks and MAPKs
RAS:GTP:inactive p-RAF complexes phosphorylate MAP2Ks
Dissociation of high activity BRAF complexes
Dissociation of moderate activity BRAF complexes
Dissociation of oncogenic RAS:RAF complex
Dissociation of paradoxically activated RAS:BRAF complexes
Homo- or heterodimerization of RAF downstream of mutant RAS
Moderate kinase activity BRAF mutants:RAS:GTP homo/heterodimerize
Inactive BRAF mutants:mutant RAS:GTP bind RAF1
Activated BRAF recruits MAP2Ks and MAPKs to the endosome
Activated BRAF phosphorylates MAP2K dimers downstream of RAP1 and NGF
Dissociation of phosphorylated MAP2Ks and MAPKs
MAP2Ks phosphorylate MAPKs downstream of BRAF and NGF
BRAF autophosphorylates downstream of RAP1 and NGF
Raf dimer inhibitors bind RAF heterodimers
Dissociation of RAS:RAF1 mutant complex
MAP2Ks and MAPKs bind to the activated mutant RAF1 complex
Phosphorylation of RAF1 mutants
RAF1 mutants show enhanced heterodimerization with BRAF
MAP2Ks phosphorylate MAPKs downstream of RAF1 mutants
RAF1 mutant complexes phosphorylate MAP2K dimer
Dual mechanism MAP2K inhibitors bind MAP2Ks
Dual mechanism MAPK inhibitors bind MAPKs
Single mechanism MAP2K inhibitors bind phosphorylated MAP2Ks
Single mechanism MAPK inhibitors bind phosphorylated MAPK
MRAS:SHOC2:PPP1CC dephosphorylates inactive RAFs
SHOC2 M173I disrupts the SHOC2:MRAS:PP1 complex
Mutant MRAS:SHOC2:PPP1CC complexes dephosphorylate inactive RAFs
UniProt record for human BRAF (P15056)
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BRAF phosphorylates MAP2K1 (MEK1) and thereby activates the MAP kinase signal transduction pathway.
"Phosphorylates MAP2K1, and thereby activates the MAP kinase signal transduction pathway"
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BRAF is an ATP-dependent protein serine/threonine kinase (EC 2.7.11.1).
"L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP"