MAP4K4

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MAP4K4
4obo.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases MAP4K4, FLH21957, HEL-S-31, HGK, MEKKK4, NIK, mitogen-activated protein kinase kinase kinase kinase 4
External IDs MGI: 1349394 HomoloGene: 7442 GeneCards: MAP4K4
RNA expression pattern
PBB GE MAP4K4 206571 s at fs.png

PBB GE MAP4K4 218181 s at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001242559
NM_001242560
NM_004834
NM_145686
NM_145687

NM_001252200
NM_001252201
NM_001252202
NM_008696

RefSeq (protein)

NP_001229488
NP_001229489
NP_004825
NP_663719
NP_663720

Location (UCSC) Chr 2: 101.7 – 101.89 Mb Chr 1: 39.9 – 40.03 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

Mitogen-activated protein kinase kinase kinase kinase 4 is an enzyme that in humans is encoded by the MAP4K4 gene.[3][4][5][6]

Function[edit]

The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase has been shown to specifically activate MAPK8/JNK. The activation of MAPK8 by this kinase is found to be inhibited by the dominant-negative mutants of MAP3K7/TAK1, MAP2K4/MKK4, and MAP2K7/MKK7, which suggests that this kinase may function through the MAP3K7-MAP2K4-MAP2K7 kinase cascade, and mediate the TNF-alpha signaling pathway. Alternatively spliced transcript variants encoding different isoforms have been identified.[6] A recent study showed that MAP4K4 is a direct kinase of LATS1/2 and thus regulates the Hippo pathway effectors YAP and TAZ. [7][8]

Interactions[edit]

MAP4K4 has been shown to interact with NCK1[5] and CD29.[9]

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ Yao Z, Zhou G, Wang XS, Brown A, Diener K, Gan H, Tan TH (Jan 1999). "A novel human STE20-related protein kinase, HGK, that specifically activates the c-Jun N-terminal kinase signaling pathway". The Journal of Biological Chemistry. 274 (4): 2118–25. doi:10.1074/jbc.274.4.2118. PMID 9890973. 
  4. ^ Ishikawa K, Nagase T, Suyama M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Jun 1998). "Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro". DNA Research. 5 (3): 169–76. doi:10.1093/dnares/5.3.169. PMID 9734811. 
  5. ^ a b Su YC, Han J, Xu S, Cobb M, Skolnik EY (Mar 1997). "NIK is a new Ste20-related kinase that binds NCK and MEKK1 and activates the SAPK/JNK cascade via a conserved regulatory domain". The EMBO Journal. 16 (6): 1279–90. doi:10.1093/emboj/16.6.1279. PMC 1169726Freely accessible. PMID 9135144. 
  6. ^ a b "Entrez Gene: MAP4K4 mitogen-activated protein kinase kinase kinase kinase 4". 
  7. ^ Meng, Zhipeng; Moroishi, Toshiro; Mottier-Pavie, Violaine; Plouffe, Steven W.; Hansen, Carsten G.; Hong, Audrey W.; Park, Hyun Woo; Mo, Jung-Soon; Lu, Wenqi (2015-10-05). "MAP4K family kinases act in parallel to MST1/2 to activate LATS1/2 in the Hippo pathway". Nature Communications. 6: 8357. doi:10.1038/ncomms9357. PMC 4600732Freely accessible. PMID 26437443. 
  8. ^ Meng, Zhipeng; Moroishi, Toshiro; Guan, Kun-Liang (2016-01-01). "Mechanisms of Hippo pathway regulation". Genes & Development. 30 (1): 1–17. doi:10.1101/gad.274027.115. ISSN 0890-9369. PMC 4701972Freely accessible. PMID 26728553. 
  9. ^ Poinat P, De Arcangelis A, Sookhareea S, Zhu X, Hedgecock EM, Labouesse M, Georges-Labouesse E (Apr 2002). "A conserved interaction between beta1 integrin/PAT-3 and Nck-interacting kinase/MIG-15 that mediates commissural axon navigation in C. elegans". Current Biology. 12 (8): 622–31. doi:10.1016/S0960-9822(02)00764-9. PMID 11967148. 

Further reading[edit]