MAP kinase kinase kinase

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Mitogen-activated protein kinase kinase kinase
Identifiers
EC number 2.7.11.25
CAS number 146702-84-3
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
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.