MAP3K3

From Wikipedia, the free encyclopedia

Main article: MAP kinase kinase kinase

Mitogen-activated protein kinase kinase kinase 3

PDB rendering based on 2c60.

Available structures: 2c60, 2o2v, 2pph

Identifiers

Symbol(s)

MAP3K3; MAPKKK3; MEKK3

External IDs

OMIM: 602539 MGI: 1346874 HomoloGene: 69110

Gene ontology
Molecular Function:	• nucleotide binding • magnesium ion binding • protein serine/threonine kinase activity • MAP kinase kinase kinase activity • signal transducer activity • protein binding • ATP binding • transferase activity
Cellular Component:	• protein complex
Biological Process:	• MAPKKK cascade • protein amino acid phosphorylation • positive regulation of I-kappaB kinase/NF-kappaB cascade • protein amino acid autophosphorylation

RNA expression pattern

More reference expression data

Orthologs

Human

Mouse

Refseq

NM_002401 (mRNA)
NP_002392 (protein)

NM_011947 (mRNA)
NP_036077 (protein)

Location

Chr 17: 59.05 - 59.13 Mb

Chr 11: 105.9 - 105.97 Mb

Pubmed search

[1]

[2]

Mitogen-activated protein kinase kinase kinase 3, also known as MAP3K3, is a human gene.

This gene product is a 626-amino acid polypeptide that is 96.5% identical to mouse Mekk3. Its catalytic domain is closely related to those of several other kinases, including mouse Mekk2, tobacco NPK, and yeast Ste11. Northern blot analysis revealed a 4.6-kb transcript that appears to be ubiquitously expressed. This protein directly regulates the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by activating SEK and MEK1/2 respectively; it does not regulate the p38 pathway. In cotransfection assays, it enhanced transcription from a nuclear factor kappa-B (NFKB)-dependent reporter gene, consistent with a role in the SAPK pathway. Alternatively spliced transcript variants encoding distinct isoforms have been observed.^[1]

[edit] References

^ Entrez Gene: MAP3K3 mitogen-activated protein kinase kinase kinase 3.

[edit] Further reading

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. PMID 8125298.
Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery.". Genome Res. 6 (9): 791–806. PMID 8889548.
Ellinger-Ziegelbauer H, Brown K, Kelly K, Siebenlist U (1997). "Direct activation of the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by an inducible mitogen-activated protein Kinase/ERK kinase kinase 3 (MEKK) derivative.". J. Biol. Chem. 272 (5): 2668–74. PMID 9006902.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.". Gene 200 (1-2): 149–56. PMID 9373149.
Fanger GR, Widmann C, Porter AC, et al. (1998). "14-3-3 proteins interact with specific MEK kinases.". J. Biol. Chem. 273 (6): 3476–83. PMID 9452471.
Chao TH, Hayashi M, Tapping RI, et al. (2000). "MEKK3 directly regulates MEK5 activity as part of the big mitogen-activated protein kinase 1 (BMK1) signaling pathway.". J. Biol. Chem. 274 (51): 36035–8. PMID 10593883.
Yang J, Boerm M, McCarty M, et al. (2000). "Mekk3 is essential for early embryonic cardiovascular development.". Nat. Genet. 24 (3): 309–13. doi:10.1038/73550. PMID 10700190.
Sun W, Kesavan K, Schaefer BC, et al. (2001). "MEKK2 associates with the adapter protein Lad/RIBP and regulates the MEK5-BMK1/ERK5 pathway.". J. Biol. Chem. 276 (7): 5093–100. doi:10.1074/jbc.M003719200. PMID 11073940.
Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination.". Genome Res. 10 (11): 1788–95. PMID 11076863.
Wiemann S, Weil B, Wellenreuther R, et al. (2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.". Genome Res. 11 (3): 422–35. doi:10.1101/gr.154701. PMID 11230166.
Simpson JC, Wellenreuther R, Poustka A, et al. (2001). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing.". EMBO Rep. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMID 11256614.
Yang J, Lin Y, Guo Z, et al. (2001). "The essential role of MEKK3 in TNF-induced NF-kappaB activation.". Nat. Immunol. 2 (7): 620–4. doi:10.1038/89769. PMID 11429546.
Che W, Lerner-Marmarosh N, Huang Q, et al. (2002). "Insulin-like growth factor-1 enhances inflammatory responses in endothelial cells: role of Gab1 and MEKK3 in TNF-alpha-induced c-Jun and NF-kappaB activation and adhesion molecule expression.". Circ. Res. 90 (11): 1222–30. PMID 12065326.
Lee CM, Onésime D, Reddy CD, et al. (2002). "JLP: A scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors.". Proc. Natl. Acad. Sci. U.S.A. 99 (22): 14189–94. doi:10.1073/pnas.232310199. PMID 12391307.
Adams DG, Sachs NA, Vaillancourt RR (2002). "Phosphorylation of the stress-activated protein kinase, MEKK3, at serine 166.". Arch. Biochem. Biophys. 407 (1): 103–16. PMID 12392720.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932.
Matsuda A, Suzuki Y, Honda G, et al. (2003). "Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways.". Oncogene 22 (21): 3307–18. doi:10.1038/sj.onc.1206406. PMID 12761501.
Nakamura K, Johnson GL (2003). "PB1 domains of MEKK2 and MEKK3 interact with the MEK5 PB1 domain for activation of the ERK5 pathway.". J. Biol. Chem. 278 (39): 36989–92. doi:10.1074/jbc.C300313200. PMID 12912994.
Huang Q, Yang J, Lin Y, et al. (2004). "Differential regulation of interleukin 1 receptor and Toll-like receptor signaling by MEKK3.". Nat. Immunol. 5 (1): 98–103. doi:10.1038/ni1014. PMID 14661019.
Samanta AK, Huang HJ, Bast RC, Liao WS (2004). "Overexpression of MEKK3 confers resistance to apoptosis through activation of NFkappaB.". J. Biol. Chem. 279 (9): 7576–83. doi:10.1074/jbc.M311659200. PMID 14662759.