MAP2K4

Dual-specificity mitogen-activated protein kinase kinase 4 is an enzyme that in humans is encoded by the MAP2K4 gene.[5]

Main article: Mitogen-activated protein kinase kinase

MAP2K4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3ALN, 3ALO, 3VUT
Identifiers
Aliases	MAP2K4, JNKK, JNKK1, MAPKK4, MEK4, MKK4, PRKMK4, SAPKK-1, SAPKK1, SEK1, SERK1, SKK1, mitogen-activated protein kinase kinase 4
External IDs	OMIM: 601335 MGI: 1346869 HomoloGene: 48159 GeneCards: MAP2K4
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17p12 Start 12,020,829 bp[1] End 12,143,830 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11 B3|11 40.53 cM Start 65,688,243 bp[2] End 65,788,297 bp[2]
Gene ontology Molecular function • transferase activity • protein kinase activity • nucleotide binding • kinase activity • GO:0001948 protein binding • protein tyrosine kinase activity • ATP binding • MAP kinase kinase activity • JUN kinase kinase activity • protein serine/threonine kinase activity • mitogen-activated protein kinase kinase kinase binding Cellular component • cytoplasm • cell nucleus • dendrite cytoplasm • cytosol • perikaryon • axon Biological process • phosphorylation • MAPK cascade • protein phosphorylation • cellular response to mechanical stimulus • response to wounding • peptidyl-tyrosine phosphorylation • signal transduction • negative regulation of motor neuron apoptotic process • apoptotic process • cell growth involved in cardiac muscle cell development • cellular response to sorbitol • positive regulation of smooth muscle cell apoptotic process • JNK cascade • positive regulation of protein phosphorylation • positive regulation of neuron apoptotic process • positive regulation of DNA replication • activation of JUN kinase activity • positive regulation of apoptotic process • positive regulation of nitric-oxide synthase biosynthetic process • regulation of mitotic cell cycle • signal transduction by protein phosphorylation • stress-activated protein kinase signaling cascade • activation of protein kinase activity • regulation of apoptotic process • activation of MAPK activity • Fc-epsilon receptor signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	6416	26398
Ensembl	ENSG00000065559	ENSMUSG00000033352
UniProt	P45985	P47809
RefSeq (mRNA)	NM_001281435 NM_003010	NM_009157 NM_001316367 NM_001316368 NM_001316369 NM_001362739 NM_001362740
RefSeq (protein)	NP_001268364 NP_003001	NP_001303296 NP_001303297 NP_001303298 NP_033183 NP_001349668 NP_001349669
Location (UCSC)	Chr 17: 12.02 – 12.14 Mb	Chr 11: 65.69 – 65.79 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

MAP2K4 encodes a dual-specificity kinase that belongs to the Ser/Thr protein kinase family. MAP2K4 phosphorylates MAP kinases in response to various environmental stresses or mitogenic stimuli. MAPK8/JNK1, MAPK9/JNK2, and MAPK14/p38 are substrates for MAP2K4, but MAPK1/ERK2 and MAPK3/ERK1 are not phosphorylated by MAP2K4. MAP2K4 is phosphorylated and activated by MAP3K1/MEKK1. Knockout mouse studies suggest roles for MAP2K4 in mediating T cell development and liver organogenesis.[6]

Interactions

MAP2K4 has been shown to interact with:

• MAP3K1, [7],
• FLNC,[8]
• MAPK8,[9][10][11][12][13]
• MAPK8IP3[14][15] and
• AKT1.[10]

References

1. GRCh38: Ensembl release 89: ENSG00000065559 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000033352 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Lin A, Minden A, Martinetto H, Claret FX, Lange-Carter C, Mercurio F, Johnson GL, Karin M (May 1995). "Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2". Science. 268 (5208): 286–90. Bibcode:1995Sci...268..286L. doi:10.1126/science.7716521. PMID 7716521.
6. "Entrez Gene: MAP2K4 mitogen-activated protein kinase kinase 4".
7. Xia Y, Wu Z, Su B, Murray B, Karin M (November 1998). "JNKK1 organizes a MAP kinase module through specific and sequential interactions with upstream and downstream components mediated by its amino-terminal extension". Genes & Development. 21 (21): 3369–81. doi:10.1101/gad.12.21.3369. PMID 9808624.
8. Marti, A; Luo Z; Cunningham C; Ohta Y; Hartwig J; Stossel T P; Kyriakis J M; Avruch J (January 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. ISSN 0021-9258. PMID 9006895.
9. Lee, Clement M; Onésime Djamila; Reddy C Damodara; Dhanasekaran N; Reddy E Premkumar (October 2002). "JLP: A scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors". Proc. Natl. Acad. Sci. U.S.A. United States. 99 (22): 14189–94. Bibcode:2002PNAS...9914189L. doi:10.1073/pnas.232310199. ISSN 0027-8424. PMC 137859. PMID 12391307.
10. Park, Hee-Sae; Kim Mi-Sung; Huh Sung-Ho; Park Jihyun; Chung Jongkyeong; Kang Sang Sun; Choi Eui-Ju (January 2002). "Akt (protein kinase B) negatively regulates SEK1 by means of protein phosphorylation". J. Biol. Chem. United States. 277 (4): 2573–8. doi:10.1074/jbc.M110299200. ISSN 0021-9258. PMID 11707464.
11. 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. ISSN 0021-9258. PMID 11279118.
12. Tournier, C; Whitmarsh A J; Cavanagh J; Barrett T; Davis R J (July 1997). "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proc. Natl. Acad. Sci. U.S.A. UNITED STATES. 94 (14): 7337–42. Bibcode:1997PNAS...94.7337T. doi:10.1073/pnas.94.14.7337. ISSN 0027-8424. PMC 23822. PMID 9207092.
13. Cheng, J; Yang J; Xia Y; Karin M; Su B (April 2000). "Synergistic interaction of MEK kinase 2, c-Jun N-terminal kinase (JNK) kinase 2, and JNK1 results in efficient and specific JNK1 activation". Mol. Cell. Biol. UNITED STATES. 20 (7): 2334–42. doi:10.1128/MCB.20.7.2334-2342.2000. ISSN 0270-7306. PMC 85399. PMID 10713157.
14. Ito, M; Yoshioka K; Akechi M; Yamashita S; Takamatsu N; Sugiyama K; Hibi M; Nakabeppu Y; Shiba T; Yamamoto K I (November 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. doi:10.1128/mcb.19.11.7539. ISSN 0270-7306. PMC 84763. PMID 10523642.
15. Matsuura, Hiroshi; Nishitoh Hideki; Takeda Kohsuke; Matsuzawa Atsushi; Amagasa Teruo; Ito Michihiko; Yoshioka Katsuji; Ichijo Hidenori (October 2002). "Phosphorylation-dependent scaffolding role of JSAP1/JIP3 in the ASK1-JNK signaling pathway. A new mode of regulation of the MAP kinase cascade". J. Biol. Chem. United States. 277 (43): 40703–9. doi:10.1074/jbc.M202004200. ISSN 0021-9258. PMID 12189133.

Further reading

• Lin, A (2006). "The JNK Signaling Pathway (Molecular Biology Intelligence Unit)". Landes Bioscience. 1: 1–97. ISBN 978-1587061202.