RAF1 Protein, Human (Y340D, Y341D, sf9, GST)

RAF1, a serine/threonine-protein kinase, serves as a pivotal regulatory link connecting membrane-associated Ras GTPases to the MAPK/ERK cascade, playing a decisive role in determining cellular fate decisions such as proliferation, differentiation, apoptosis, survival, and oncogenic transformation. Upon activation, RAF1 initiates a MAPK cascade involving the sequential phosphorylation of dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and extracellular signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). The phosphorylated form of RAF1, facilitated by PAK1, phosphorylates BAD/Bcl2-antagonist of cell death at 'Ser-75' and adenylyl cyclases (ADCY2, ADCY5, and ADCY6), activating them. Additionally, RAF1 phosphorylates PPP1R12A, inhibiting its phosphatase activity. Beyond its role in the MAPK cascade, RAF1 can activate NF-kB and inhibit key signaling molecules involved in motility, apoptosis, proliferation, and angiogenesis. It exerts anti-apoptotic effects by translocating to the mitochondria, binding BCL2, and displacing BAD/Bcl2-antagonist of cell death. Furthermore, RAF1 regulates Rho signaling, migration, wound healing, and is implicated in oncogenic transformation by repressing the tight junction protein occludin (OCLN). Notably, RAF1 restrains caspase activation in response to specific stimuli, including Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation.