A-Raf kinase (A-Raf)

A-Raf kinase is one of three isoforms in the RAF kinase family (A-Raf, B-Raf, c-Raf/Raf-1), which are serine/threonine protein kinases functioning as critical intermediates in the RAS-RAF-MEK-ERK (MAPK) signaling cascade[2][4][6]. RAF kinases transmit signals from cell surface receptors such as receptor tyrosine kinases via Ras activation, leading ultimately to activation of MEK1/2, then ERK1/2, driving cell proliferation, survival, and differentiation[2][3][6]. Compared to other isoforms, A-Raf displays weaker kinase activity and is less responsive to activation by oncogenic Ras or Src, partly due to unique amino acid substitutions in its Ras-binding domain and N-region[4]. Although A-Raf shares structural similarity and regulatory mechanisms with c-Raf/Raf-1, its physiological and pathological functions are less well understood. Importantly, mutations in A-Raf are rare in human cancers, but A-Raf may contribute to tumorigenic signaling driven by upstream oncogenic events and participates in regulation of the MAPK pathway[2][4][6]. Selective targeting of A-Raf is not currently established in clinical practice.

Other names

ARAFv-raf murine sarcoma 3611 viral oncogene homolog AA-Raf proto-oncogeneserine/threonine-protein kinase A-Raf

Inhibition of kinase activity (by small molecule inhibitors in broader RAF inhibition); Downregulation of the RAF-MEK-ERK signal transduction pathway