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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 ]
Activated Ras then activates the protein kinase activity of a RAF kinase. [4] The RAF kinase phosphorylates and activates a MAPK/ERK Kinase (MEK1 or MEK2). The MEK phosphorylates and activates a mitogen-activated protein kinase (MAPK). RAF and MAPK/ERK are both serine/threonine-specific protein kinases. MEK is a serine/tyrosine/threonine kinase.
The Raf kinase inhibitor protein (RKIP) is a kinase inhibitor protein, that regulates many signaling pathways within the cell. [1] RKIP is a member of the phosphatidylethanolamine-binding protein family and has displayed disruptive regulation on the Raf-1- MEK 1/2, ERK 1/2 and NF-kappaB signalling pathways, by interaction with the Raf-1 kinase.
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.
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 ...
Serine/threonine-protein kinase A-Raf or simply A-Raf is an enzyme that in humans is encoded by the ARAF gene. [5] A-Raf is a member of the Raf kinase family of serine/threonine-specific protein kinases. [6] Compared to the other members of this family (Raf-1 and B-Raf), very little is known about A-Raf.
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]