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RAF is an acronym for Rapidly Accelerated Fibrosarcoma. [12] RAF kinases participate in the RAS-RAF-MEK-ERK signal transduction cascade, also referred to as the mitogen-activated protein kinase (MAPK) cascade. [11] Activation of RAF kinases requires interaction with RAS-GTPases. The three RAF kinase family members are: A-RAF; B-RAF; c-Raf
RAF proto-oncogene serine/threonine-protein kinase, also known as proto-oncogene c-RAF or simply c-Raf or even Raf-1, is an enzyme [4] that in humans is encoded by the RAF1 gene. [ 5 ] [ 6 ] The c-Raf protein is part of the ERK1/2 pathway as a MAP kinase (MAP3K) that functions downstream of the Ras subfamily of membrane associated GTPases. [ 7 ]
As discussed below, many additional targets for phosphorylation by MAPK were later found, and the protein was renamed "mitogen-activated protein kinase" (MAPK). The series of kinases from RAF to MEK to MAPK is an example of a protein kinase cascade. Such series of kinases provide opportunities for feedback regulation and signal amplification.
B-Raf is a 766-amino acid, regulated signal transduction serine/threonine-specific protein kinase.Broadly speaking, it is composed of three conserved domains characteristic of the Raf kinase family: conserved region 1 (CR1), a Ras-GTP-binding [11] self-regulatory domain, conserved region 2 (CR2), a serine-rich hinge region, and conserved region 3 (CR3), a catalytic protein kinase domain that ...
For example, KSR1 and KSR2 are actually MAP3 kinases and related to the Raf proteins. [37] Although KSRs alone display negligible MAP3 kinase activity, KSR proteins can still participate in the activation of Raf kinases by forming side-to-side heterodimers with them, providing an allosteric pair to turn on each enzymes. [38]
Cytoplasmic Serine/threonine kinases and their regulatory subunits: Raf kinase, and cyclin-dependent kinases (through overexpression). malignant melanoma, papillary thyroid cancer, colorectal cancer, and ovarian cancer [31] involved in organism development, cell cycle regulation, cell proliferation, differentiation, cells survival, and ...
There are three main classes of MAP Kinases and are regulated by their respective MAPKKKs. These MAP kinases include the extracellular regulated kinases (ERKs), the c-Jun N-terminal Kinases (JNKs), and the p38 MAP kinase. The ERKs are regulated by the Raf family of MAPKKKs and are responsible for cell growth, differentiation, and meiosis.
Ras is typically activated by growth hormones through receptor tyrosine kinases and GRB2/SOS, but may also receive other signals. ERKs are known to activate many transcription factors, such as ELK1, [1] and some downstream protein kinases. Disruption of the ERK pathway is common in cancers, especially Ras, c-Raf, and receptors such as HER2.