MAP kinase kinase kinase

MEKK4EC 2.7.11.25MAP kinase kinase kinasesMAP3 kinasesMAP3KMAP3KsMAPK/ERK kinase kinase 4MAPKK kinaseMAPKKKsMEKK protein 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.wikipedia
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MAPK/ERK pathway

MAPK/ERKMAPKMAPK signaling pathway
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.
It can now activate MAP3K (e.g., Raf), which activates MAP2K, which activates MAPK.

C-Raf

RAF1Raf-1Raf
Similarly to many other MAPKKKs, c-Raf is a multidomain protein, with several additional domains to aid the regulation of its catalytic activity.

Mitogen-activated protein kinase

MAPKMAP kinasemitogen-activated protein kinases
MAP2 kinases in turn, are also activated by phosphorylation, by a number of different upstream serine-threonine kinases (MAP3 kinases).

C-Jun N-terminal kinases

JNKc-Jun N-terminal kinasec-Jun N-terminal kinase (JNK)
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.

MAP2K4

MKK4JNKK1
MEKK1 activates MAPK8/JNK by phosphorylation of its activator SEK1(MAP2K4).

MAP3K3

MEKK3
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.

P38 mitogen-activated protein kinases

p38p38 MAPKp38 MAP kinase
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

TAK1MAP3K7 (TAK1)MP3K7
MAP3K7(TAK1) participates in regulation of transcription by transforming growth factor-beta (TGF-beta).

Transforming growth factor beta

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

ASK1

MAP3K5apoptosis signal-inducing kinase 1apoptosis signal-regulating kinase 1

MAP3K8

MAP3K14

NF-κB inducing kinaseNIK