IndraLab

Statements

RAF1 binds BRAF and RAS. 30 / 30
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sparser
"As predicted, these compounds blocked Sos-mediated nucleotide exchange and decreased the binding of Ras to both B-Raf and C-Raf."
25323927
sparser
"Activated GTP bound Ras binds the upstream protein kinases Raf-1 and B-Raf."
15067337
sparser
"In the presence of oncogenic RAS proteins, kinase-silent BRAF forms a complex with CRAF and lead to hyperactivation of the CRAF/MEK/ERK cascade (Fig.  xref ) [ xref ]."
26498038
sparser
"Moreover, BRAF inhibitors drive RAS-dependent BRAF binding to CRAF, CRAF activation, and MEK-ERK signaling in oncogenic RAS [ xref ] revealing a paradigm of BRAF-mediated signaling that promotes tumour progression with clinical implications [ xref ] and highlighting the importance of understanding pathway signaling in clinical practice and of genotyping tumours prior to administering BRAF-selective drugs, to identify patients who are likely to respond and also to identify patients who may experience adverse effects such as increased invasion [ xref ]."
25932043
sparser
"Figure 3A confirms that CRAF must interact with RAS to promote BRAF:CRAF dimerization."
26885666
sparser
"Figure 3B: A key finding of the original study is that RAS interaction with both CRAF and BRAF is required to induce BRAF:CRAF dimerization in the presence of a BRAF inhibitor."
26885666
sparser
"We agree that one of the key findings of the original paper was that both BRAF and CRAF must bind to RAS to create the proposed stable complex, so have included this additional experiment, reported in Figure 3B of the original study, into the revised Registered Report."
26885666
sparser
"Both B-Raf and C-Raf were constitutively bound to oncogenic Ras and contributed to Ras-dependent ERK activation."
23893412
sparser
"Ras binding to B-Raf and C-Raf were both subject to inhibition by the cAMP-dependent protein kinase PKA."
23893412
sparser
"As predicted, treatment with 12 decreased the association of B-Raf and C-Raf with Ras ( xref )."
24256730
sparser
"PKA inhibited the binding of Ras to both C-Raf and B-Raf through phosphorylations of C-Raf at Ser-259 and B-Raf at Ser-365, respectively."
23893412
sparser
"These complex interactions of RAS, BRAF, and CRAF explain the existence and function of inactivating BRAF mutations in cancer cells, which superficially seem to be contrary to natural selection."
22649091
sparser
"This intracellular signal induces a decrease of both Raf-1 and B-Raf affinities for activated Ras as well as the activation of Rap1."
11510412
sparser
"We show that drugs that selectively inhibit BRAF drive RAS-dependent BRAF binding to CRAF, CRAF activation, and MEK–ERK signaling."
20141835
sparser
"Rheb has been reported to inhibit the Raf-dependent MAPK pathway through the interaction of the Ras-binding domain of BRaf or cRaf in a rapamycin-insensitive manner ( xref xref – xref )."
19258434
sparser
"RAS-GTP binds to the serine/threonine kinases B-RAF and C-RAF."
29861875
sparser
"The point mutation at 64, in combination with additional point mutations at either position 65 or 71, resulted in a protein which failed to interact with either PI-3 kinase or neurofibromin, though these Ras mutants effectively bound both Raf-1 and B-raf."
7630628
sparser
"In the presence of oncogenic RAS proteins, kinase-impaired BRAF forms a complex with CRAF, which leads to hyperactivation of the CRAF/MEK/ERK cascade [ xref , xref ]."
27699178
sparser
"The compounds bind to a region of the Switch 2 region and block nucleotide exchange and therefore decrease the binding of RAS to both BRAF and CRAF."
33394740
sparser
"After activation of RasGDP proteins by one of its GEFs, RasGTP can bind and activate both C-Raf and B-Raf, though RasGTP has a higher affinity towards C-Raf than B-Raf."
31945453
sparser
"Wild-type BRAF binds to CRAF in a RAS-dependent manner and although this binding is weak, it leads to CRAF activation ( xref )."
20141835
sparser
"To confirm the essential role of RAS, we show that a CRAF mutant ( R89L CRAF) that cannot bind to RAS ( xref ) did not bind to BRAF ( xref A and xref A) and the corresponding mutant of BRAF ( R188L BRAF) did not bind to CRAF ( xref B and see xref B)."
20141835
sparser
"Active RAS interacts with many downstream mediators, most importantly by binding to the RAS-binding domain of BRAF or Raf-1 proto-oncogene, serine/threonine kinase (RAF1)."
28067895
sparser
"N-RAS mutations have been identified in 15%–20% of cutaneous melanoma and are presumed to be one of the important drivers of oncogenesis. xref A somatic mutation in the N-RAS gene causes constitutive activation of the N-RAS protein, which leads to the successive activation of downstream serine/threonine kinases, which promote cell cycle progression, cellular transformation, and enhanced cell survival. xref The overexpression of growth factor receptors, such as epidermal growth factor receptor, c-Met, platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor, and c-KIT is also implicated as a mechanism of cellular growth and transformation in RAS-driven melanomas. xref , xref The most important downstream mediators of activated RAS are the serine/threonine kinases B-RAF and C-RAF, which are activated following RAS binding."
23226069
sparser
"These results suggest that there is a subtle structural difference in requirements for the interaction of Ras with Raf-1 and B-Raf."
8687465
sparser
"Selective inhibition of B-Raf drives oncogenic RAS-dependent BRAF binding to C-Raf, CRAF activation and mitogen-activated protein kinase kinase (MEK)-extracellular signal regulated kinase (ERK) signalling, revealing another paradigm of BRAF-mediated signalling that promotes tumour progression [ xref ]."
21129151
sparser
"These data suggested that increased binding of class 3 BRAF mutants to activated RAS is associated with formation of more heterodimers of mutant BRAF and wild-type CRAF."
28783719
sparser
"In vitro studies have shown that in the presence of oncogenic RAS proteins, kinase-impaired BRAF forms a complex with CRAF and leads to hyperactivation of the CRAF/MEK/ERK cascade, suggesting MEK inhibitors or CRAF inhibitors may benefit patients with concomitant kinase-impaired BRAF mutation and activating RAS mutation [ xref , xref ]."
29228562
reach
"Furthermore, in PC9 cells, treatment with alphaC-IN inhibitor AZ, but not with the alphaC-OUT inhibitor PB, resulted in formation of the CRAF, BRAF, and RAS complex, an effect that was abolished after pretreatment with GEF (XREF_SUPPLEMENTARY)."
27523909
sparser
"We established an essential role for RAS in these responses by showing that its depletion blocked MEK/ERK activation and if BRAF or CRAF were unable to bind to RAS, they did not form dimers."
22169110