Accepted name: mitogen-activated protein kinase kinase kinase
Reaction: ATP + a protein = ADP + a phosphoprotein
Other name(s): cMos; cRaf; MAPKKK; MAP3K; MAP kinase kinase kinase; MEKK; MEKK1; MEKK2; MEKK3; MEK kinase; Mil/Raf; MLK-like mitogen-activated protein triple kinase; MLTK; MLTKa; MLTKb; REKS; STK28
Systematic name: ATP:protein phosphotransferase (MAPKKKK-activated)
Comments: This enzyme phosphorylates and activates its downstream protein kinase, EC, mitogen-activated protein kinase kinase (MAPKK) but requires MAPKKKK for activation. Some members of this family can be activated by p21-activated kinases (PAK/STE20) or Ras. While c-Raf and c-Mos activate the classical MAPK/ERK pathway, MEKK1 and MEKK2 preferentially activate the c-Jun N-terminal protein kinase(JNK)/stress-activated protein kinase (SAPK) pathway [2]. Mitogen-activated protein kinase (MAPK) signal transduction pathways are among the most widespread mechanisms of cellular regulation. Mammalian MAPK pathways can be recruited by a wide variety of stimuli including hormones (e.g. insulin and growth hormone), mitogens (e.g. epidermal growth factor and platelet-derived growth factor), vasoactive peptides (e.g. angiotensin-II and endothelin), inflammatory cytokines of the tumour necrosis factor (TNF) family and environmental stresses such as osmotic shock, ionizing radiation and ischaemic injury.
1.  Wang, X.S., Diener, K., Jannuzzi, D., Trollinger, D., Tan, T.H., Lichenstein, H., Zukowski, M. and Yao, Z. Molecular cloning and characterization of a novel protein kinase with a catalytic domain homologous to mitogen-activated protein kinase kinase kinase. J. Biol. Chem. 271 (1996) 31607–31611. [PMID: 8940179]
2.  Gotoh, I., Adachi, M. and Nishida, E. Identification and characterization of a novel MAP kinase kinase kinase, MLTK. J. Biol. Chem. 276 (2001) 4276–4286. [PMID: 11042189]
3.  Vojtek, A.B., Hollenberg, S.M. and Cooper, J.A. Mammalian Ras interacts directly with the serine/threonine kinase Raf. Cell 74 (1993) 205–214. [PMID: 8334704]
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