Molecular Classification
Serine/threonine-protein kinase, Enzyme, MAP3K, RAF family kinase
Other Names
RAF1 proto-oncogene serine/threonine kinase, c-Raf, Raf-1
Disease Roles
CancerLung cancerNon-small cell lung carcinoma

C-Raf kinase Overview

C-Raf kinase, also known as RAF1 or Raf-1 proto-oncogene serine/threonine kinase, is a key serine/threonine-protein kinase in the RAF family. It acts as a principal component of the mitogen-activated protein kinase (MAPK) pathway—specifically the ERK1/2 signaling cascade—serving as a MAP3K that initiates downstream signaling events critical for cell fate decisions. Its activation requires binding to active GTP-bound Ras at cellular membranes, conformational change from closed/inactive to open/active state upon Ras binding, and phosphorylation at specific sites. Aberrant regulation or overexpression of c-Raf is implicated in various cancers and developmental disorders. Resistance mechanisms against BRAF inhibitors often involve compensatory activation of C-Raf. Inhibitors targeting RAF kinases can block MEK/ERK activation but may paradoxically increase signaling under certain conditions.

Mechanism of Action

RAF kinase inhibitors block MEK/ERK activation.

Biological Functions

Signal transduction
Cell proliferation
Cell differentiation
Cell survival
Apoptosis
Cell motility
Cell migration
Wound healing
T-cell development
B-cell development
ERK1/2 signaling cascade regulation

Disease Associations

Cancer
Lung cancer
Non-small cell lung carcinoma
Liver cancer
Prostate cancer
Developmental disorders
Tumor initiation
Tumor progression
Metastasis
Resistance mechanisms

Safety Considerations

  • Paradoxical increase in signaling under certain conditions due to complex feedback/dimerization mechanisms involving wild-type versus mutant forms.
  • Effectiveness of targeting only c-Raf remains debated because both its kinase-dependent and independent functions contribute variably depending on tumor context—especially relevant for KRAS-mutant tumors where c-Raf’s non-catalytic roles may be essential.

Interacting Drugs

RAF kinase inhibitors