MAP2K1

Main article: Mitogen-activated protein kinase kinase

Mitogen-activated protein kinase kinase 1
PDB rendering based on 1s9j.
Available structures PDB 1S9J, 2P55, 3DV3, 3DY7, 3E8N, 3EQB, 3EQC, 3EQD, 3EQF, 3EQG, 3EQH, 3EQI, 3MBL
Identifiers
Symbols	MAP2K1; MAPKK1; MEK1; MKK1; PRKMK1
External IDs	OMIM: 176872 MGI: 1346866 HomoloGene: 2063 GeneCards: MAP2K1 Gene
EC number	2.7.12.2
Gene Ontology Molecular function • nucleotide binding • protein kinase activity • protein serine/threonine kinase activity • MAP kinase kinase activity • protein tyrosine kinase activity • receptor signaling protein tyrosine phosphatase activity • protein binding • ATP binding • Ras GTPase binding • mitogen-activated protein kinase kinase kinase binding Cellular component • soluble fraction • cytoplasm • Golgi apparatus • cytosol • cytosol • microtubule • plasma membrane • cell cortex • dendrite cytoplasm • axon part • perikaryon • perinuclear region of cytoplasm Biological process • MAPKKK cascade • activation of MAPKK activity • activation of MAPK activity • toll-like receptor signaling pathway • MyD88-dependent toll-like receptor signaling pathway • MyD88-dependent toll-like receptor signaling pathway • MyD88-independent toll-like receptor signaling pathway • MyD88-independent toll-like receptor signaling pathway • regulation of vascular smooth muscle contraction • cellular component movement • chemotaxis • response to oxidative stress • cell cycle arrest • mitosis • signal transduction • epidermal growth factor receptor signaling pathway • small GTPase mediated signal transduction • Ras protein signal transduction • axon guidance • Toll signaling pathway • negative regulation of cell proliferation • insulin receptor signaling pathway • neuron differentiation • keratinocyte differentiation • positive regulation of cell migration • positive regulation of Ras GTPase activity • melanosome transport • positive regulation of transcription elongation from RNA polymerase II promoter • negative regulation of homotypic cell-cell adhesion • toll-like receptor 1 signaling pathway • toll-like receptor 2 signaling pathway • toll-like receptor 3 signaling pathway • toll-like receptor 4 signaling pathway • innate immune response • positive regulation of cell differentiation • vesicle transport along microtubule • nerve growth factor receptor signaling pathway • Golgi inheritance • response to axon injury • neuron projection morphogenesis • cell motility • protein heterooligomerization • response to glucocorticoid stimulus • stress-activated MAPK cascade • placenta blood vessel development • labyrinthine layer development • cellular senescence Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5604	26395
Ensembl	ENSG00000169032	ENSMUSG00000004936
UniProt	Q02750	Q3TMJ8
RefSeq (mRNA)	NM_002755.3	NM_008927.3
RefSeq (protein)	NP_002746.1	NP_032953.1
Location (UCSC)	Chr 15: 66.68 – 66.78 Mb	Chr 9: 64.03 – 64.1 Mb
PubMed search	[1]	[2]

Dual specificity mitogen-activated protein kinase kinase 1 is an enzyme that in humans is encoded by the MAP2K1 gene.^[1][2]

Function

The protein encoded by this gene is a member of the dual specificity protein kinase family, which acts as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon activation by a wide variety of extra- and intracellular signals. As an essential component of the MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as proliferation, differentiation, transcription regulation and development.^[3]

Interactions

MAP2K1 has been shown to interact with C-Raf,^[4] Phosphatidylethanolamine binding protein 1,^[4] MAP2K1IP1,^[5][6] GRB10,^[7] MAPK3,^{[6][8][9][10][11]} MAPK8IP3,^[12][13] MAPK1^{[4][5][14][15][16][17]} MP1,^[6] and MAP3K1.^[18]

References

1. ^ Rampoldi L, Zimbello R, Bortoluzzi S, Tiso N, Valle G, Lanfranchi G, Danieli GA (Mar 1998). "Chromosomal localization of four MAPK signaling cascade genes: MEK1, MEK3, MEK4 and MEKK5". Cytogenet Cell Genet 78 (3-4): 301–3. doi:10.1159/000134677. PMID 9465908. 
2. ^ Zheng CF, Guan KL (Jun 1993). "Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2". J Biol Chem 268 (15): 11435–9. PMID 8388392. 
3. ^ "Entrez Gene: MAP2K1 mitogen-activated protein kinase kinase 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5604. 
4. ^ ^{a b c} Yeung, K; Janosch P, McFerran B, Rose D W, Mischak H, Sedivy J M, Kolch W (May. 2000). "Mechanism of suppression of the Raf/MEK/extracellular signal-regulated kinase pathway by the raf kinase inhibitor protein". Mol. Cell. Biol. (UNITED STATES) 20 (9): 3079–85. doi:10.1128/MCB.20.9.3079-3085.2000. PMC 85596. PMID 10757792. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=85596. 
5. ^ ^{a b} Wunderlich, W; Fialka I, Teis D, Alpi A, Pfeifer A, Parton R G, Lottspeich F, Huber L A (Feb. 2001). "A novel 14-kilodalton protein interacts with the mitogen-activated protein kinase scaffold mp1 on a late endosomal/lysosomal compartment". J. Cell Biol. (United States) 152 (4): 765–76. doi:10.1083/jcb.152.4.765. PMC 2195784. PMID 11266467. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2195784. 
6. ^ ^{a b c} Schaeffer, H J; Catling A D, Eblen S T, Collier L S, Krauss A, Weber M J (Sep. 1998). "MP1: a MEK binding partner that enhances enzymatic activation of the MAP kinase cascade". Science (UNITED STATES) 281 (5383): 1668–71. doi:10.1126/science.281.5383.1668. PMID 9733512. 
7. ^ Nantel, A; Mohammad-Ali K, Sherk J, Posner B I, Thomas D Y (Apr. 1998). "Interaction of the Grb10 adapter protein with the Raf1 and MEK1 kinases". J. Biol. Chem. (UNITED STATES) 273 (17): 10475–84. doi:10.1074/jbc.273.17.10475. PMID 9553107. 
8. ^ Marti, A; Luo Z, Cunningham C, Ohta Y, Hartwig J, Stossel T P, Kyriakis J M, Avruch J (Jan. 1997). "Actin-binding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor necrosis factor-alpha activation of SAPK in melanoma cells". J. Biol. Chem. (UNITED STATES) 272 (5): 2620–8. doi:10.1074/jbc.272.5.2620. PMID 9006895. 
9. ^ Butch, E R; Guan K L (Feb. 1996). "Characterization of ERK1 activation site mutants and the effect on recognition by MEK1 and MEK2". J. Biol. Chem. (UNITED STATES) 271 (8): 4230–5. doi:10.1074/jbc.271.8.4230. PMID 8626767. 
10. ^ Yung, Y; Yao Z, Hanoch T, Seger R (May. 2000). "ERK1b, a 46-kDa ERK isoform that is differentially regulated by MEK". J. Biol. Chem. (UNITED STATES) 275 (21): 15799–808. doi:10.1074/jbc.M910060199. PMID 10748187. 
11. ^ Zheng, C F; Guan K L (Nov. 1993). "Properties of MEKs, the kinases that phosphorylate and activate the extracellular signal-regulated kinases". J. Biol. Chem. (UNITED STATES) 268 (32): 23933–9. PMID 8226933. 
12. ^ Kuboki, Y; Ito M, Takamatsu N, Yamamoto K I, Shiba T, Yoshioka K (Dec. 2000). "A scaffold protein in the c-Jun NH2-terminal kinase signaling pathways suppresses the extracellular signal-regulated kinase signaling pathways". J. Biol. Chem. (UNITED STATES) 275 (51): 39815–8. doi:10.1074/jbc.C000403200. PMID 11044439. 
13. ^ Ito, M; Yoshioka K, Akechi M, Yamashita S, Takamatsu N, Sugiyama K, Hibi M, Nakabeppu Y, Shiba T, Yamamoto K I (Nov. 1999). "JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway". Mol. Cell. Biol. (UNITED STATES) 19 (11): 7539–48. PMC 84763. PMID 10523642. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=84763. 
14. ^ Sanz-Moreno, Victoria; Casar Berta, Crespo Piero (May. 2003). "p38alpha isoform Mxi2 binds to extracellular signal-regulated kinase 1 and 2 mitogen-activated protein kinase and regulates its nuclear activity by sustaining its phosphorylation levels". Mol. Cell. Biol. (United States) 23 (9): 3079–90. doi:10.1128/MCB.23.9.3079-3090.2003. PMC 153192. PMID 12697810. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=153192. 
15. ^ Robinson, Fred L; Whitehurst Angelique W, Raman Malavika, Cobb Melanie H (Apr. 2002). "Identification of novel point mutations in ERK2 that selectively disrupt binding to MEK1". J. Biol. Chem. (United States) 277 (17): 14844–52. doi:10.1074/jbc.M107776200. PMID 11823456. 
16. ^ Xu Be, Be; Stippec S, Robinson F L, Cobb M H (Jul. 2001). "Hydrophobic as well as charged residues in both MEK1 and ERK2 are important for their proper docking". J. Biol. Chem. (United States) 276 (28): 26509–15. doi:10.1074/jbc.M102769200. PMID 11352917. 
17. ^ Chen, Z; Cobb M H (May. 2001). "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2". J. Biol. Chem. (United States) 276 (19): 16070–5. doi:10.1074/jbc.M100681200. PMID 11279118. 
18. ^ Karandikar, M; Xu S, Cobb M H (Dec. 2000). "MEKK1 binds raf-1 and the ERK2 cascade components". J. Biol. Chem. (UNITED STATES) 275 (51): 40120–7. doi:10.1074/jbc.M005926200. PMID 10969079. 

Further reading

• Wu J, Michel H, Rossomando A, Haystead T, Shabanowitz J, Hunt DF, Sturgill TW. (1992). "Renaturation and partial peptide sequencing of mitogen-activated protein kinase (MAP kinase) activator from rabbit skeletal muscle". Biochem J. 285 (3): 701–5. PMC 1132850. PMID 1379797. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1132850. 
• Rossomando AJ, Dent P, Sturgill TW, Marshak DR. (1994). "Mitogen-activated protein kinase kinase 1 (MKK1) is negatively regulated by threonine phosphorylation". Mol Cell Biol 14 (3): 1594–602. PMC 358518. PMID 8114697. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=358518. 
• Seger R, Krebs EG (1995). "The MAPK signaling cascade.". FASEB J. 9 (9): 726–35. PMID 7601337. 
• Joseph AM, Kumar M, Mitra D (2005). "Nef: "necessary and enforcing factor" in HIV infection.". Curr. HIV Res. 3 (1): 87–94. doi:10.2174/1570162052773013. PMID 15638726. 
• Tanaka S, Nakamura K, Takahasi N, Suda T (2006). "Role of RANKL in physiological and pathological bone resorption and therapeutics targeting the RANKL-RANK signaling system.". Immunol. Rev. 208: 30–49. doi:10.1111/j.0105-2896.2005.00327.x. PMID 16313339. 
• Stove V, Verhasselt B (2006). "Modelling thymic HIV-1 Nef effects.". Curr. HIV Res. 4 (1): 57–64. doi:10.2174/157016206775197583. PMID 16454711. 
• Galabova-Kovacs G, Kolbus A, Matzen D, et al. (2006). "ERK and beyond: insights from B-Raf and Raf-1 conditional knockouts.". Cell Cycle 5 (14): 1514–8. doi:10.4161/cc.5.14.2981. PMID 16861903. 

External links

• GeneReviews/NCBI/NIH/UW entry on Noonan syndrome
• GeneReviews/NCBI/NIH/UW entry on Cardiofaciocutaneous Syndrome