RAF1: a proto-oncogenic TKL kinase of the RAF family. Functions downstream of the Ras family of membrane associated GTPases to which it binds directly. Once activated Raf-1 can phosphorylate and activate MEK1/2, which in turn phosphorylate and activate ERK1/2. Acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MEK1/2) and the extracellular signal-regulated kinases (ERK1/2). RAF1, subsequent to phosphorylation by PAK1, phosphorylates BAD (Bcl2-antagonist of cell death) at S75. Phosphorylates adenylyl cyclases ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity. Phosphorylates TNNT2 (cardiac muscle troponin T). Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (ASK1 and MST2), proliferation and angiogenesis (RB1). Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation.
Protein type: Kinase, protein; Oncoprotein; Protein kinase, TKL; Protein kinase, Ser/Thr (non-receptor); EC 2.7.11.1; TKL group; RAF family
Cellular Component: Golgi apparatus; mitochondrion; membrane; cytoplasm; plasma membrane; pseudopodium; nucleus; cytosol
Molecular Function: identical protein binding; mitogen-activated protein kinase kinase binding; metal ion binding; nucleotide binding; protein kinase activity; transferase activity; protein serine/threonine kinase activity; protein binding; Ras GTPase binding; MAP kinase kinase kinase activity; protein heterodimerization activity; receptor signaling protein activity; transferase activity, transferring phosphorus-containing groups; kinase activity; ATP binding
Biological Process: activation of MAPKK activity; nerve growth factor receptor signaling pathway; somatic stem cell maintenance; MAPKKK cascade; intermediate filament cytoskeleton organization and biogenesis; signal transduction; protein amino acid phosphorylation; positive regulation of peptidyl-serine phosphorylation; negative regulation of cell proliferation; response to hypoxia; cell glucose homeostasis; positive regulation of transcription from RNA polymerase II promoter; positive regulation of protein amino acid phosphorylation; cell differentiation; phosphorylation; negative regulation of protein complex assembly; negative regulation of apoptosis
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