MAP kinase kinase kinase

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:
 * MAP3K1 (aka MEKK1)
 * MAP3K2
 * MAP3K3 (aka MEKK3)
 * MAP3K4
 * MAP3K5 (aka ASK1)
 * MAP3K6 (aka ASK2)
 * MAP3K7 (aka MEKK7) (aka TAK1)
 * MAP3K8 (aka TPL2 or Tpl2)
 * MAP3K9
 * MAP3K10
 * MAP3K11 (aka MEKK11) (aka MLK3)
 * MAP3K12 (aka MUK)
 * MAP3K13 (aka LZK)
 * MAP3K14
 * MAP3K15
 * MAP3K16 (aka TAO1 or TAOK1)
 * MAP3K17 (aka TAO2 or TAOK2)
 * RAF1
 * BRAF
 * ARAF
 * ZAK (aka MLTK)

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).

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.

MAP3K7(TAK1)participate in regulation of transcription by transforming growth factor-beta (TGF-beta).