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MAP kinase kinase kinase (or MAP3K or MEKK), also known as Raf, is a serine/threonine-specific protein kinase which acts upon MAP kinase kinase. In humans, there are at least 19 genes which encode MAP kinase kinase kinases:

Mitogen-activated protein kinase kinase kinase
EC number2.7.11.25
CAS number146702-84-3
IntEnzIntEnz view
ExPASyNiceZyme view
MetaCycmetabolic pathway
PDB structuresRCSB PDB PDBe PDBsum

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).

MEKK1 activates MAPK8/JNK by phosphorylation of its activator SEK1(MAP2K4).[1]

MAP3K3 directly regulates the MAPK8/JNK and extracellular signal-regulated protein kinase (ERK) pathways by activating SEK and MEK1/2 respectively; it does not regulate the p38 pathway.[2]

MAP3K7(TAK1) participates in regulation of transcription by transforming growth factor-beta (TGF-beta).[3]

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  1. ^ Yan M, Dai T, Deak JC, Kyriakis JM, Zon LI, Woodgett JR, Templeton DJ (1994). "Activation of stress-activated protein kinase by MEKK1 phosphorylation of its activator SEK1". Nature. 372 (6508): 798–800. doi:10.1038/372798a0. PMID 7997270.
  2. ^ Ellinger-Ziegelbauer H, Brown K, Kelly K, Siebenlist U (January 1997). "Direct activation of the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by an inducible mitogen-activated protein Kinase/ERK kinase kinase 3 (MEKK) derivative". The Journal of Biological Chemistry. 272 (5): 2668–74. doi:10.1074/jbc.272.5.2668. PMID 9006902.
  3. ^ Yamaguchi K, Shirakabe K, Shibuya H, Irie K, Oishi I, Ueno N, Taniguchi T, Nishida E, Matsumoto K (December 1995). "Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction". Science. 270 (5244): 2008–11. doi:10.1126/science.270.5244.2008. PMID 8533096.

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