MAP3K11

Mitogen-activated protein kinase kinase kinase 11
Identifiers
Symbols	MAP3K11 ; MEKK11; MLK-3; MLK3; PTK1; SPRK
External IDs	OMIM: 600050 MGI: 1346880 HomoloGene: 37618 ChEMBL: 2708 GeneCards: MAP3K11 Gene
EC number	2.7.11.25
Gene ontology Molecular function • protein kinase activity • protein serine/threonine kinase activity • JUN kinase kinase kinase activity • protein tyrosine kinase activity • protein binding • ATP binding • mitogen-activated protein kinase kinase binding • mitogen-activated protein kinase kinase kinase binding • identical protein binding • protein homodimerization activity • Rac GTPase binding Cellular component • cytoplasm • centrosome • microtubule • membrane Biological process • activation of MAPK activity • protein phosphorylation • microtubule-based process • JNK cascade • activation of JNKK activity • activation of JUN kinase activity • cell death • cell proliferation • peptidyl-tyrosine phosphorylation • positive regulation of JUN kinase activity • positive regulation of neuron apoptotic process • positive regulation of JNK cascade • protein autophosphorylation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4296	26403
Ensembl	ENSG00000173327	ENSMUSG00000004054
UniProt	Q16584	Q80XI6
RefSeq (mRNA)	NM_002419	NM_022012
RefSeq (protein)	NP_002410	NP_071295
Location (UCSC)	Chr 11: 65.6 – 65.62 Mb	Chr 19: 5.69 – 5.7 Mb
PubMed search

Mitogen-activated protein kinase kinase kinase 11 is an enzyme that in humans is encoded by the MAP3K11 gene.^[1][2]

Function

The protein encoded by this gene is called MLK3 and it is a member of the serine/threonine kinase family. This kinase contains a SH3 domain and a leucine zipper-basic motif. This kinase preferentially activates MAPK8/JNK kinase, and functions as a positive regulator of JNK signaling pathway. This kinase can directly phosphorylate, and activates JNK and p38, and is found to be involved in the transcription activity of AP1 mediated by Rho family GTPases and CDC42.^[3][4]

Interactions

MAP3K11 has been shown to interact with:

• AKT1,^[5]
• CDC42,^[6][7]
• MAPK8IP1,^[8]
• MAPK8IP2,^[8] and
• SH3RF1.^[9]

References

1. Smith CM, Ma NS, Nowak NJ, Shows TB, Gerhard DS (October 1997). "A 3-Mb Contig from D11S987 to MLK3, a Gene-Rich Region in 11q13". Genome Res 7 (8): 835–42. doi:10.1101/gr.7.8.835. PMC 310665. PMID 9267807.
2. Ing YL, Leung IW, Heng HH, Tsui LC, Lassam NJ (June 1994). "MLK-3: identification of a widely-expressed protein kinase bearing an SH3 domain and a leucine zipper-basic region domain". Oncogene 9 (6): 1745–50. PMID 8183572.
3. Kant S, Swat W, Zhang S, Zhang ZY, Neel BG, Flavell RA, Davis RJ (Oct 1, 2011). "TNF-stimulated MAP kinase activation mediated by a Rho family GTPase signaling pathway". Genes Dev 25 (19): 2069–78. doi:10.1101/gad.17224711. PMC 3197205. PMID 21979919.
4. "Entrez Gene: MAP3K11 mitogen-activated protein kinase kinase kinase 11".
5. Barthwal MK, Sathyanarayana P, Kundu CN, Rana B, Pradeep A, Sharma C, Woodgett JR, Rana A (February 2003). "Negative regulation of mixed lineage kinase 3 by protein kinase B/AKT leads to cell survival". J. Biol. Chem. 278 (6): 3897–902. doi:10.1074/jbc.M211598200. PMID 12458207.
6. 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.
7. Böck BC, Vacratsis PO, Qamirani E, Gallo KA (May 2000). "Cdc42-induced activation of the mixed-lineage kinase SPRK in vivo. Requirement of the Cdc42/Rac interactive binding motif and changes in phosphorylation". J. Biol. Chem. 275 (19): 14231–41. doi:10.1074/jbc.275.19.14231. PMID 10799501.
8. 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.
9. Figueroa C, Tarras S, Taylor J, Vojtek AB (November 2003). "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.

Further reading

• van de Bovenkamp M, Nottet HS, Pereira CF (2003). "Interactions of human immunodeficiency virus-1 proteins with neurons: possible role in the development of human immunodeficiency virus-1-associated dementia". Eur. J. Clin. Invest. 32 (8): 619–27. doi:10.1046/j.1365-2362.2002.01029.x. PMID 12190962.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• 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.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Tanaka S, Hanafusa H (1998). "Guanine-nucleotide exchange protein C3G activates JNK1 by a ras-independent mechanism. JNK1 activation inhibited by kinase negative forms of MLK3 and DLK mixed lineage kinases". J. Biol. Chem. 273 (3): 1281–4. doi:10.1074/jbc.273.3.1281. PMID 9430657.
• Leung IW, Lassam N (1999). "Dimerization via tandem leucine zippers is essential for the activation of the mitogen-activated protein kinase kinase kinase, MLK-3". J. Biol. Chem. 273 (49): 32408–15. doi:10.1074/jbc.273.49.32408. PMID 9829970.
• Merritt SE, Mata M, Nihalani D, Zhu C, Hu X, Holzman LB (1999). "The mixed lineage kinase DLK utilizes MKK7 and not MKK4 as substrate". J. Biol. Chem. 274 (15): 10195–202. doi:10.1074/jbc.274.15.10195. PMID 10187804.
• Yasuda J, Whitmarsh AJ, Cavanagh J, Sharma M, Davis RJ (2000). "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.
• Kelkar N, Gupta S, Dickens M, Davis RJ (2000). "Interaction of a Mitogen-Activated Protein Kinase Signaling Module with the Neuronal Protein JIP3". Mol. Cell. Biol. 20 (3): 1030–43. doi:10.1128/MCB.20.3.1030-1043.2000. PMC 85220. PMID 10629060.
• Hehner SP, Hofmann TG, Ushmorov A, Dienz O, Wing-Lan Leung I, Lassam N, Scheidereit C, Dröge W, Schmitz ML (2000). "Mixed-Lineage Kinase 3 Delivers CD3/CD28-Derived Signals into the IκB Kinase Complex". Mol. Cell. Biol. 20 (7): 2556–68. doi:10.1128/MCB.20.7.2556-2568.2000. PMC 85472. PMID 10713178.
• Böck BC, Vacratsis PO, Qamirani E, Gallo KA (2000). "Cdc42-induced activation of the mixed-lineage kinase SPRK in vivo. Requirement of the Cdc42/Rac interactive binding motif and changes in phosphorylation". J. Biol. Chem. 275 (19): 14231–41. doi:10.1074/jbc.275.19.14231. PMID 10799501.
• Leung IW, Lassam N (2001). "The kinase activation loop is the key to mixed lineage kinase-3 activation via both autophosphorylation and hematopoietic progenitor kinase 1 phosphorylation". J. Biol. Chem. 276 (3): 1961–7. doi:10.1074/jbc.M004092200. PMID 11053428.
• Svensson AC, Raudsepp T, Larsson C, Di Cristofano A, Chowdhary B, La Mantia G, Rask L, Andersson G (2001). "Chromosomal distribution, localization and expression of the human endogenous retrovirus ERV9". Cytogenet. Cell Genet. 92 (1–2): 89–96. doi:10.1159/000056875. PMID 11306803.
• Zhang H, Gallo KA (2002). "Autoinhibition of mixed lineage kinase 3 through its Src homology 3 domain". J. Biol. Chem. 276 (49): 45598–603. doi:10.1074/jbc.M107176200. PMID 11590155.
• Lambert JM, Karnoub AE, Graves LM, Campbell SL, Der CJ (2002). "Role of MLK3-mediated activation of p70 S6 kinase in Rac1 transformation". J. Biol. Chem. 277 (7): 4770–7. doi:10.1074/jbc.M109379200. PMID 11713255.
• Chadee DN, Yuasa T, Kyriakis JM (2002). "Direct Activation of Mitogen-Activated Protein Kinase Kinase Kinase MEKK1 by the Ste20p Homologue GCK and the Adapter Protein TRAF2". Mol. Cell. Biol. 22 (3): 737–49. doi:10.1128/MCB.22.3.737-749.2002. PMC 133545. PMID 11784851.
• Vacratsis PO, Phinney BS, Gage DA, Gallo KA (2002). "Identification of in vivo phosphorylation sites of MLK3 by mass spectrometry and phosphopeptide mapping". Biochemistry 41 (17): 5613–24. doi:10.1021/bi016075c. PMID 11969422.