MAP3K10

Mitogen-activated protein kinase kinase kinase 10
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2RF0​
Identifiers
Symbols	MAP3K10 ; MEKK10; MLK2; MST
External IDs	OMIM: 600137 MGI: 1346879 HomoloGene: 1834 IUPHAR: 2070 ChEMBL: 2873 GeneCards: MAP3K10 Gene
EC number	2.7.11.25
Gene ontology Molecular function • transcription corepressor activity • protein kinase activity • protein serine/threonine kinase activity • JUN kinase kinase kinase activity • ATP binding • protein homodimerization activity • bHLH transcription factor binding Cellular component • cytoplasm Biological process • apoptotic process • signal transduction • smoothened signaling pathway • JNK cascade • activation of JNKK activity • activation of JUN kinase activity • peptidyl-serine phosphorylation • peptidyl-threonine phosphorylation • positive regulation of apoptotic process • negative regulation of sequence-specific DNA binding transcription factor activity • positive regulation of JUN kinase activity • negative regulation of transcription, DNA-templated • positive regulation of JNK cascade • protein autophosphorylation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4294	269881
Ensembl	ENSG00000130758	ENSMUSG00000040390
UniProt	Q02779	Q66L42
RefSeq (mRNA)	NM_002446	NM_001081292
RefSeq (protein)	NP_002437	NP_001074761
Location (UCSC)	Chr 19: 40.19 – 40.22 Mb	Chr 7: 27.66 – 27.67 Mb
PubMed search

Mitogen-activated protein kinase kinase kinase 10 is an enzyme that in humans is encoded by the MAP3K10 gene.^[1][2][3]

Function

The protein encoded by this gene is a member of the serine/threonine kinase family. This kinase has been shown to activate MAPK8/JNK and MKK4/SEK1, and this kinase itself can be phoshorylated, and thus activated by JNK kinases. This kinase functions preferentially on the JNK signaling pathway, and is reported to be involved in nerve growth factor (NGF) induced neuronal apoptosis.^[3]

Interactions

MAP3K10 has been shown to interact with:

• CDC42,^[4]
• Huntingtin,^[5]
• KIF3A,^[4]
• MAPK8IP1,^[6]
• MAPK8IP2,^[6] and
• NEUROD1.^[7]

References

1. Dorow DS, Devereux L, Tu GF, Price G, Nicholl JK, Sutherland GR, Simpson RJ (February 1996). "Complete nucleotide sequence, expression, and chromosomal localisation of human mixed-lineage kinase 2". Eur J Biochem 234 (2): 492–500. doi:10.1111/j.1432-1033.1995.492_b.x. PMID 8536694.
2. Katoh M, Hirai M, Sugimura T, Terada M (May 1995). "Cloning and characterization of MST, a novel (putative) serine/threonine kinase with SH3 domain". Oncogene 10 (7): 1447–51. PMID 7731697.
3. "Entrez Gene: MAP3K10 mitogen-activated protein kinase kinase kinase 10".
4. Nagata Ki, Puls A, Futter C, Aspenstrom P, Schaefer E, Nakata T, Hirokawa N, Hall A (January 1998). "The MAP kinase kinase kinase MLK2 co-localizes with activated JNK along microtubules and associates with kinesin superfamily motor KIF3". EMBO J. 17 (1): 149–58. doi:10.1093/emboj/17.1.149. PMC 1170366. PMID 9427749.
5. Liu YF, Dorow D, Marshall J (June 2000). "Activation of MLK2-mediated signaling cascades by polyglutamine-expanded huntingtin". J. Biol. Chem. 275 (25): 19035–40. doi:10.1074/jbc.C000180200. PMID 10801775.
6. Yasuda J, Whitmarsh AJ, Cavanagh J, Sharma M, Davis RJ (October 1999). "The JIP group of mitogen-activated protein kinase scaffold proteins". Mol. Cell. Biol. 19 (10): 7245–54. doi:10.1128/mcb.19.10.7245. PMC 84717. PMID 10490659.
7. Marcora E, Gowan K, Lee JE (August 2003). "Stimulation of NeuroD activity by huntingtin and huntingtin-associated proteins HAP1 and MLK2". Proc. Natl. Acad. Sci. U.S.A. 100 (16): 9578–83. doi:10.1073/pnas.1133382100. PMC 170960. PMID 12881483.

Further reading

• Gallo KA, Mark MR, Scadden DT, Wang Z, Gu Q, Godowski PJ (1994). "Identification and characterization of SPRK, a novel src-homology 3 domain-containing proline-rich kinase with serine/threonine kinase activity". J. Biol. Chem. 269 (21): 15092–100. PMID 8195146.
• Dorow DS, Devereux L, Dietzsch E, De Kretser T (1993). "Identification of a new family of human epithelial protein kinases containing two leucine/isoleucine-zipper domains". Eur. J. Biochem. 213 (2): 701–10. doi:10.1111/j.1432-1033.1993.tb17810.x. PMID 8477742.
• Hirai Si, Katoh M, Terada M, Kyriakis JM, Zon LI, Rana A, Avruch J, Ohno S (1997). "MST/MLK2, a member of the mixed lineage kinase family, directly phosphorylates and activates SEK1, an activator of c-Jun N-terminal kinase/stress-activated protein kinase". J. Biol. Chem. 272 (24): 15167–73. doi:10.1074/jbc.272.24.15167. PMID 9182538.
• Hirai Si, Noda K, Moriguchi T, Nishida E, Yamashita A, Deyama T, Fukuyama K, Ohno S (1998). "Differential activation of two JNK activators, MKK7 and SEK1, by MKN28-derived nonreceptor serine/threonine kinase/mixed lineage kinase 2". J. Biol. Chem. 273 (13): 7406–12. doi:10.1074/jbc.273.13.7406. PMID 9516438.
• Rasmussen RK, Ji H, Eddes JS, Moritz RL, Reid GE, Simpson RJ, Dorow DS (1998). "Two-dimensional electrophoretic analysis of mixed lineage kinase 2 N-terminal domain binding proteins". Electrophoresis 19 (5): 809–17. doi:10.1002/elps.1150190535. PMID 9629920.
• Rasmussen RK, Rusak J, Price G, Robinson PJ, Simpson RJ, Dorow DS (1998). "Mixed-lineage kinase 2-SH3 domain binds dynamin and greatly enhances activation of GTPase by phospholipid". Biochem. J. 335 (Pt 1): 119–24. PMC 1219759. PMID 9742220.
• Liu YF, Dorow D, Marshall J (2000). "Activation of MLK2-mediated signaling cascades by polyglutamine-expanded huntingtin". J. Biol. Chem. 275 (25): 19035–40. doi:10.1074/jbc.C000180200. PMID 10801775.
• Hartley JL, Temple GF, Brasch MA (2001). "DNA Cloning Using In Vitro Site-Specific Recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
• Savinainen A, Garcia EP, Dorow D, Marshall J, Liu YF (2001). "Kainate receptor activation induces mixed lineage kinase-mediated cellular signaling cascades via post-synaptic density protein 95". J. Biol. Chem. 276 (14): 11382–6. doi:10.1074/jbc.M100190200. PMID 11152698.
• Xu Z, Maroney AC, Dobrzanski P, Kukekov NV, Greene LA (2001). "The MLK Family Mediates c-Jun N-Terminal Kinase Activation in Neuronal Apoptosis". Mol. Cell. Biol. 21 (14): 4713–24. doi:10.1128/MCB.21.14.4713-4724.2001. PMC 87148. PMID 11416147.
• Poy MN, Yang Y, Rezaei K, Fernström MA, Lee AD, Kido Y, Erickson SK, Najjar SM (2002). "CEACAM1 regulates insulin clearance in liver". Nat. Genet. 30 (3): 270–6. doi:10.1038/ng840. PMID 11850617.
• Akbarzadeh S, Ji H, Frecklington D, Marmy-Conus N, Mok YF, Bowes L, Devereux L, Linsenmeyer M, Simpson RJ, Dorow DS (2002). "Mixed lineage kinase 2 interacts with clathrin and influences clathrin-coated vesicle trafficking". J. Biol. Chem. 277 (39): 36280–7. doi:10.1074/jbc.M204626200. PMID 12105200.
• Figueroa C, Tarras S, Taylor J, Vojtek AB (2004). "Akt2 negatively regulates assembly of the POSH-MLK-JNK signaling complex". J. Biol. Chem. 278 (48): 47922–7. doi:10.1074/jbc.M307357200. PMID 14504284.
• Eckey M, Tenbaum SP, Muñoz A, Baniahmad A (2004). "Mixed lineage kinase 2 enhances trans-repression of Alien and nuclear receptors". Mol. Cell. Endocrinol. 213 (1): 71–8. doi:10.1016/j.mce.2003.10.035. PMID 15062575.
• Jaffe AB, Hall A, Schmidt A (2005). "Association of CNK1 with Rho guanine nucleotide exchange factors controls signaling specificity downstream of Rho". Curr. Biol. 15 (5): 405–12. doi:10.1016/j.cub.2004.12.082. PMID 15753034.
• Kollers S, Musilova P, Rubes J, Rocha D (2007). "Comparative mapping reveals multiple rearrangements between pig chromosome 6 and human 19q13". Anim. Genet. 37 (6): 595–6. doi:10.1111/j.1365-2052.2006.01516.x. PMID 17121608.