||This enzyme phosphorylates and activates its downstream protein kinase, EC 188.8.131.52, 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 . 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.
||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]
||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]
||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]