MAP kinase kinase kinase

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Mitogen-activated protein kinase kinase kinase
EC number
CAS number 146702-84-3
IntEnz IntEnz view
ExPASy NiceZyme view
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum

MAP kinase kinase kinase (or MAP3K or MEKK) is a serine/threonine-specific protein kinase which acts upon MAP kinase kinase.

In humans there are at least 19 genes:

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

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  1. ^ Yan M, et al. (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, et al. (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". J Biol Chem. 272 (5): 2668–2674. doi:10.1074/jbc.272.5.2668. PMID 9006902. 
  3. ^ Yamaguchi K, et al. (1995). "Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction". Science 270 (5244): 2008–2011. doi:10.1126/science.270.5244.2008. PMID 8533096.