B-Raf protein kinase and C-Raf protein kinase (BRAF and CRAF (also known as RAF1))

B-Raf protein kinase (BRAF) and C-Raf protein kinase (CRAF, also known as RAF1) are members of the RAF family of serine/threonine-protein kinases that act as direct effectors of RAS GTPases within the RAS-RAF-MEK-ERK signaling pathway[2][3][4][5]. Upon activation by GTP-bound RAS, BRAF and CRAF undergo conformational changes, dimerize, and activate downstream MEK1/2 kinases, which further phosphorylate ERK1/2, ultimately regulating gene expression and controlling cell proliferation, differentiation, survival, and apoptosis[2][4]. Mutations, particularly the V600E substitution in BRAF, are well-established drivers in various human cancers, most notably melanoma, and germline mutations in BRAF or CRAF are causative for certain developmental syndromes known as RASopathies[2][3][4][5]. RAF inhibitors such as vemurafenib and dabrafenib are used clinically in cancers harboring BRAF V600 mutations, but therapeutic challenges such as paradoxical MAPK pathway activation and resistance mechanisms are significant considerations[6].

Other names

BRAFCRAFRAF1 (for CRAF)v-Raf murine sarcoma viral oncogene homolog B1 (BRAF)RAF proto-oncogene serine/threonine-protein kinase (both)Raf kinaseSerine/threonine-protein kinase B-Raf/C-Raf

Inhibition of kinase activity (prevents phosphorylation of downstream targets MEK1/2) Blockade of RAF dimerization (for some drugs) Disruption of RAS-RAF-MEK-ERK signaling pathway