RAS-BRAF signaling complex (RAS-BRAF)

The RAS-BRAF signaling complex is a critical molecular assembly in the mitogen-activated protein kinase (MAPK) pathway, primarily responsible for transmitting extracellular signals from cell surface receptors to the nucleus [1][2]. This complex forms when active, GTP-bound RAS isoforms (such as KRAS, NRAS, or HRAS) recruit BRAF to the plasma membrane, facilitating its dimerization and subsequent activation of the downstream MEK/ERK cascade [3][4]. Dysregulation of this complex, often through oncogenic mutations in RAS or BRAF (notably the BRAF V600E mutation), leads to constitutive signaling that drives uncontrolled cell proliferation and survival in numerous malignancies, including melanoma and colorectal cancer [2][5]. Therapeutic strategies targeting this complex include small-molecule inhibitors that bind the BRAF kinase domain or disrupt the physical interaction between RAS and RAF [4][6]. However, a significant challenge in targeting this complex is the phenomenon of paradoxical activation, where certain inhibitors can inadvertently stimulate MAPK signaling in cells with wild-type BRAF and mutant RAS [6][7]. Ongoing research focuses on next-generation paradox-breaker inhibitors and bifunctional degraders to overcome resistance and improve clinical outcomes [7][8].

Other names

RAS-RAF complexRAS-BRAF interactionRAS-BRAF dimerMAPK signaling complexRat sarcoma-B-Raf proto-oncogene signaling complexRas GTPase-B-Raf serine/threonine-protein kinase complex

Inhibition of BRAF kinase activity within the complex, disruption of RAS-mediated RAF recruitment to the plasma membrane, and prevention of RAF dimerization [4][6].