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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.
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
Similarly, both dual-specificity MAP kinase phosphatases and MAP-specific tyrosine phosphatases bind to MAP kinases through the same docking site. [34] [35] D-motifs can even be found in certain MAPK pathway regulators and scaffolds (e.g. in the mammalian JIP proteins). [citation needed] Other, less well characterised substrate-binding sites ...
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 ...
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]
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.
Ras, from "Rat sarcoma virus", is a family of related proteins that are expressed in all animal cell lineages and organs. All Ras protein family members belong to a class of protein called small GTPase, and are involved in transmitting signals within cells (cellular signal transduction).
Assembly and localization of the RAS-ERK pathway: One of the best studied signaling pathways in biology is the RAS-ERK pathway in which the RAS G-protein activates the MAPKKK RAF, which activates the MAPKK MEK1 (MAPK/ERK kinase 1), which then activates the MAPK ERK. Several scaffold proteins have been identified to be involved in this pathway ...
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