RAF kinase family (RAF)

RAF kinases are a family of serine/threonine protein kinases including ARAF, BRAF, and CRAF (RAF1). They are key components of the RAS-RAF-MEK-ERK signaling pathway regulating cell growth and proliferation. RAF kinases have a C-terminal catalytic domain and an N-terminal regulatory domain containing a RAS binding domain (RBD) and cysteine-rich domain (CRD). They are activated by RAS proteins and phosphorylate downstream kinases MEK and ERK. RAF activity is regulated by interacting proteins like RKIP and phosphorylation events. Dysregulated RAF signaling, often due to activating mutations (especially BRAF V600E), is a major driver of various cancers, including melanoma, thyroid, and colorectal cancer, and is also implicated in developmental syndromes. RAF kinases, particularly BRAF, are validated therapeutic targets in cancer, with several inhibitors developed, including Type I inhibitors targeting BRAF V600E and Type II inhibitors targeting RAF dimers.

Other names

RAF family kinasesARAFBRAFCRAFRAF1

Inhibition of RAF kinases disrupts the downstream RAS-RAF-MEK-ERK signaling pathway, inhibiting cell growth and proliferation, particularly in cancers driven by RAF mutations or dysregulation. Inhibitors can be selective for specific isoforms or mutation states (e.g., BRAF V600E) or target RAF dimers.