MAP kinase kinase kinase
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:
- MAP3K1 (aka MEKK1)
- MAP3K3 (aka MEKK3)
- MAP3K5 (aka ASK1)
- MAP3K6 (aka ASK2)
- MAP3K7 (aka MEKK7) (aka TAK1)
- MAP3K8 (aka TPL2 or Tpl2)
- MAP3K11 (aka MEKK11) (aka MLK3)
- MAP3K12 (aka MUK)
- MAP3K13 (aka LZK)
- MAP3K16 (aka TAO1 or TAOK1)
- MAP3K17 (aka TAO2 or TAOK2)
- ZAK (aka MLTK)
|Mitogen-activated protein kinase kinase kinase|
|PDB structures||RCSB 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).
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.
- 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.
- 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.
- 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.