Publication
Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF.
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- PubMed
- Retrieved
- Sep 8, 2026
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- normalized (units and labels harmonized; values unchanged)
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- ING-CIVIC-20260908-000001
Abstract
Abstract (excerpt)
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Linked entities
Linked entities (4)
How each link was made (MeSH, dictionary, registry reference, curation…) and whether it has been validated. Candidate links are not counted in entity statistics.
Validated 4
- cancerMalignant Neoplasmcivic_curation1.00
- geneBRAFcivic_curation1.00
- variantBRAF A728Vcivic_curation1.00
- variantBRAF G463Ecivic_curation1.00
Curated evidence
Evidence citing this paper (22)
- Source
- CIViC — Clinical Interpretation of Variants in Cancer
- Dataset
- CIViC evidence items
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- civic-2026-09-08
- Retrieved
- Sep 8, 2026
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- normalized (units and labels harmonized; values unchanged)
- Evidence
- expert curation
- License
- CC0 1.0
- PMID
- 15035987
- Run
- ING-CIVIC-20260908-000001
| Therapy | Cancer | Type | Level | Direction · significance | Rating (1–5) | Status | Evidence | Source |
|---|---|---|---|---|---|---|---|---|
| BRAF G463E1 | ||||||||
| (oncogenic) | Malignant NeoplasmALIAS | Oncogenic | D | Supports Oncogenicity | 3 | accepted | EID9527The BRAF mutation G463E resulted in elevated kinase activity relative to wild-type BRAF in vitro. B-RAF activity was determined using kinase dead MEK as a substrate. G463E activity was 28 times higher… (full text at CIViC) PMID 15035987 · Wan et al., 2004 · Open in CIViC | civic |
| BRAF G463V1 | ||||||||
| (oncogenic) | Malignant NeoplasmALIAS | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID9559By expressing B-RAF G463V protein in COS cells and measuring its direct MEK phosphorylation activity, these experiments showed that B-RAF G463V had a basal kinase activity 46 times higher than that of… (full text at CIViC) PMID 15035987 · Wan et al., 2004 · Open in CIViC | civic |
| BRAF G465A1 | ||||||||
| (oncogenic) | Malignant NeoplasmALIAS | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID9560By expressing B-RAF G465A protein in COS cells and measuring its direct MEK phosphorylation activity, these experiments showed that B-RAF G465A had a basal kinase activity 5 times higher than that of … (full text at CIViC) PMID 15035987 · Wan et al., 2004 · Open in CIViC | civic |
| BRAF G468A1 | ||||||||
| (oncogenic) | Malignant NeoplasmALIAS | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID9558By expressing B-RAF G468A protein in COS cells and measuring its direct MEK phosphorylation activity, these experiments showed that B-RAF G468A had a basal kinase activity 266 times higher than that o… (full text at CIViC) PMID 15035987 · Wan et al., 2004 · Open in CIViC | civic |
| BRAF N580S1 | ||||||||
| (oncogenic) | Malignant NeoplasmALIAS | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID9561By expressing B-RAF N580S protein in COS cells and measuring its direct MEK phosphorylation activity, these experiments showed that B-RAF N580S had a basal kinase activity 7 times higher than that of … (full text at CIViC) PMID 15035987 · Wan et al., 2004 · Open in CIViC | civic |
| BRAF T598I1 | ||||||||
| (oncogenic) | Malignant NeoplasmALIAS | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID9562By expressing B-RAF T598I protein in COS cells and measuring its direct MEK phosphorylation activity, these experiments showed that B-RAF T598I had a basal kinase activity 30 times higher than that of… (full text at CIViC) PMID 15035987 · Wan et al., 2004 · Open in CIViC | civic |
| BRAF V599E1 | ||||||||
| (oncogenic) | Malignant NeoplasmALIAS | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID9563By expressing B-RAF V600E (also known as V599E in the paper) protein in COS cells and measuring its direct MEK phosphorylation activity, these experiments showed that B-RAF V600E had a basal kinase ac… (full text at CIViC) PMID 15035987 · Wan et al., 2004 · Open in CIViC | civic |
| BRAF V600E1 | ||||||||
| (oncogenic) | Malignant NeoplasmALIAS | Oncogenic | D | Supports Oncogenicity | 2 | submitted | EID13055In this study, myc-tagged BRAF V600E (reported as V599E) transiently expressed in COS cells exhibited approximately 478-fold greater basal kinase activity than wild-type BRAF, constitutively activated… (full text at CIViC) PMID 15035987 · Wan et al., 2004 · Open in CIViC | civic |
| BRAF A728V1 | ||||||||
| (functional) | —UNRESOLVED | Functional | D | Supports Gain Of Function | 2 | accepted | EID7614The BRAF mutation A728V (also known as A727V) resulted in elevated kinase activity relative to wild-type BRAF in vitro, as well as increased phosphorylation of ERK1/2 in COS cells. B-RAF activity was … (full text at CIViC) PMID 15035987 · Wan et al., 2004 · Open in CIViC | civic |
| BRAF E585K1 | ||||||||
| (functional) | —UNRESOLVED | Functional | D | Supports Gain Of Function | 3 | submitted | EID9566By expressing B-RAF E585K protein in COS cells and measuring its direct MEK phosphorylation activity, these experiments showed that B-RAF E585K had a basal kinase activity 129 times higher than that o… (full text at CIViC) PMID 15035987 · Wan et al., 2004 · Open in CIViC | civic |
| BRAF F594L1 | ||||||||
| (functional) | —UNRESOLVED | Functional | D | Supports Gain Of Function | 3 | submitted | EID9567By expressing B-RAF F594L protein in COS cells and measuring its direct MEK phosphorylation activity, these experiments showed that B-RAF F594L had a basal kinase activity 60 times higher than that of… (full text at CIViC) PMID 15035987 · Wan et al., 2004 · Open in CIViC | civic |
| BRAF G469A1 | ||||||||
| (functional) | —UNRESOLVED | Functional | D | Supports Gain Of Function | 5 | submitted | EID12981BRAF p.Gly469Ala (NM_004333.6:c.1406G>C) causes increased MEK phosphorylation, increased ratio of pERK/ERK. Class 2 BRAF variant. (In PMID: 15035987 AA numbers shifted by one, AA 468 corresponds to AA… (full text at CIViC) PMID 15035987 · Wan et al., 2004 · Open in CIViC | civic |
| BRAF G469E1 | ||||||||
| (functional) | —UNRESOLVED | Functional | D | Supports Gain Of Function | 5 | submitted | EID12983BRAF p.Gly469Glu (NM_004333.6:c.1406G>A) causes increased MEK phosphorylation, increased signaling through RAF1 (CRAF), it has low kinase activity. Class 3 BRAF variant. (In PMID: 15035987 AA numbers … (full text at CIViC) PMID 15035987 · Wan et al., 2004 · Open in CIViC | civic |
| BRAF I462S1 | ||||||||
| (functional) | —UNRESOLVED | Functional | D | Supports Gain Of Function | 3 | submitted | EID9565By expressing B-RAF I462S protein in COS cells and measuring its direct MEK phosphorylation activity, these experiments showed that B-RAF I462S had a basal kinase activity 11 times higher than that of… (full text at CIViC) PMID 15035987 · Wan et al., 2004 · Open in CIViC | civic |
| BRAF K600E1 | ||||||||
| (functional) | —UNRESOLVED | Functional | D | Supports Gain Of Function | 3 | submitted | EID9572By expressing B-RAF K600E protein in COS cells and measuring its direct MEK phosphorylation activity, these experiments showed that B-RAF K600E had a basal kinase activity 138 times higher than that o… (full text at CIViC) PMID 15035987 · Wan et al., 2004 · Open in CIViC | civic |
| BRAF K601E1 | ||||||||
| (functional) | —UNRESOLVED | Functional | D | Supports Gain Of Function | 5 | submitted | EID12920BRAF p.Lys601Glu (NM_004333.6:c.1801A>G) causes increased pERK/ERK ratio. PMID 15035987 · Wan et al., 2004 · Open in CIViC | civic |
| BRAF L596V1 | ||||||||
| (functional) | —UNRESOLVED | Functional | D | Supports Gain Of Function | 3 | submitted | EID9568By expressing B-RAF L596V protein in COS cells and measuring its direct MEK phosphorylation activity, these experiments showed that B-RAF L596V had a basal kinase activity 64 times higher than that of… (full text at CIViC) PMID 15035987 · Wan et al., 2004 · Open in CIViC | civic |
| BRAF R461I1 | ||||||||
| (functional) | —UNRESOLVED | Functional | D | Supports Gain Of Function | 3 | submitted | EID9564By expressing B-RAF R461I protein in COS cells and measuring its direct MEK phosphorylation activity, these experiments showed that B-RAF R461I had a basal kinase activity 6 times higher than that of … (full text at CIViC) PMID 15035987 · Wan et al., 2004 · Open in CIViC | civic |
| BRAF V599R1 | ||||||||
| (functional) | —UNRESOLVED | Functional | D | Supports Gain Of Function | 3 | submitted | EID9571By expressing B-RAF V599R protein in COS cells and measuring its direct MEK phosphorylation activity, these experiments showed that B-RAF V599R had a basal kinase activity 244 times higher than that o… (full text at CIViC) PMID 15035987 · Wan et al., 2004 · Open in CIViC | civic |
| BRAF V600D1 | ||||||||
| (functional) | —UNRESOLVED | Functional | D | Supports Gain Of Function | 3 | submitted | EID9569By expressing B-RAF V600D (also known as V599D in the paper) protein in COS cells and measuring its direct MEK phosphorylation activity, the experiment showed that B-RAF V600D had a basal kinase activ… (full text at CIViC) PMID 15035987 · Wan et al., 2004 · Open in CIViC | civic |
| BRAF V600K2 | ||||||||
| (functional) | —UNRESOLVED | Functional | D | Supports Gain Of Function | 3 | rejected | EID9570By expressing B-RAF V600K (also known as V599K in the paper) protein in COS cells and measuring its direct MEK phosphorylation activity, these experiments showed that B-RAF V600K had a basal kinase ac… (full text at CIViC) PMID 15035987 · Wan et al., 2004 · Open in CIViC | civic |
| 〃 | —UNRESOLVED | Functional | D | Supports Gain Of Function | 5 | submitted | EID12980BRAF p.Val600Lys (NM_004333.6:c.1798_1799delinsAA) causes increased pERK/ERK ratio, and increased MEK phosphorylation. Class 1 BRAF variant. PMID 15035987 · Wan et al., 2004 · Open in CIViC | civic |