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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. In a technical sense, RAF, MEK, and MAPK are all mitogen-activated kinases ...
The mouse sarcoma virus 3611 contains a RAF kinase-related oncogene that enhances fibrosarcoma induction. 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]
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 ]
Another protein kinase, Raf-1, was shown to phosphorylate a "MAP kinase-kinase", thus qualifying as a "MAP kinase kinase kinase". [4] The MAP kinase-kinase, which activates ERK, was named "MAPK/ERK kinase" . [5] Receptor-linked tyrosine kinases, Ras, Raf, MEK, and MAPK could be fitted into a signaling cascade linking an extracellular signal to ...
Perhaps the best characterized MAP3K are the members of the oncogenic RAF family (RAF1, BRAF, ARAF), which are effectors of mitogenic ras signaling and which activate the ERK1/2 (MAPK3/MAPK1) pathway, through activation of MEK1(MAP2K1) and MEK2(MAP2K2). The JNKs are regulated by the MEKK 1/4, MLK 2/3, and ASK 1 MAPKKKs.
Erbin's C-terminal PDZ domain is able to bind to ErbB2, a protein tyrosine kinase which is often associated with poor prognosis in epidermal oncogenesis. [7] Erbin's N-terminal region has been shown to disrupt Ras to Raf binding and may be, through this action, a tumor suppressing protein.
Ras-related protein R-Ras2 is a protein that in humans is encoded by the RRAS2 gene. [5] [6] [7] Interactions. RRAS2 has been shown to interact with C-Raf. [8] [9]
GAP eventually returns Ras to its inactive state. Activation of Ras has the potential to initiate three signaling pathways downstream of Ras: Ras→Raf→MAP kinase pathway, PI3 kinase pathway, and Ral pathway. Each pathway leads to the activation of transcription factors which enter the nucleus to alter gene expression. [9]