ZAK explained

Sterile alpha motif and leucine zipper containing kinase AZK, also known as ZAK, is a human gene.^[1]

This gene is a member of the MAPKKK family of signal transduction molecules and encodes a protein with an N-terminal kinase catalytic domain, followed by a leucine zipper motif and a sterile-alpha motif (SAM). This magnesium-binding protein forms homodimers and is located in the cytoplasm. The protein mediates gamma radiation signaling leading to cell cycle arrest and activity of this protein plays a role in cell cycle checkpoint regulation in cells. The protein also has pro-apoptotic activity. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.^[2]

Interactions

ZAK has been shown to interact with ZNF33A.^[3]

References

• Antitumorigenic Effects of ZAKβ, an Alternative Splicing Isoform of ZAK . The Chinese Journal of Physiology . 61 . 1 . 25–34 . 28 February 2018 . 10.4077/CJP.2018.BAG528. Lee . Jin-Sun . 29374956 .

Further reading

• Liu TC, Huang CJ, Chu YC, etal . Cloning and expression of ZAK, a mixed lineage kinase-like protein containing a leucine-zipper and a sterile-alpha motif. . Biochem. Biophys. Res. Commun. . 274 . 3 . 811–6 . 2000 . 10924358 . 10.1006/bbrc.2000.3236 .
• Gotoh I, Adachi M, Nishida E . Identification and characterization of a novel MAP kinase kinase kinase, MLTK. . J. Biol. Chem. . 276 . 6 . 4276–86 . 2001 . 11042189 . 10.1074/jbc.M008595200 . free .
• Bloem LJ, Pickard TR, Acton S, etal . Tissue distribution and functional expression of a cDNA encoding a novel mixed lineage kinase. . J. Mol. Cell. Cardiol. . 33 . 9 . 1739–50 . 2002 . 11549352 . 10.1006/jmcc.2001.1437 .
• Gross EA, Callow MG, Waldbaum L, etal . MRK, a mixed lineage kinase-related molecule that plays a role in gamma-radiation-induced cell cycle arrest. . J. Biol. Chem. . 277 . 16 . 13873–82 . 2002 . 11836244 . 10.1074/jbc.M111994200 . free .
• Yang JJ . Mixed lineage kinase ZAK utilizing MKK7 and not MKK4 to activate the c-Jun N-terminal kinase and playing a role in the cell arrest. . Biochem. Biophys. Res. Commun. . 297 . 1 . 105–10 . 2002 . 12220515 . 10.1016/S0006-291X(02)02123-X .
• Strausberg RL, Feingold EA, Grouse LH, etal . 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 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Yang JJ . A novel zinc finger protein, ZZaPK, interacts with ZAK and stimulates the ZAK-expressing cells re-entering the cell cycle. . Biochem. Biophys. Res. Commun. . 301 . 1 . 71–7 . 2003 . 12535642 . 10.1016/S0006-291X(02)02980-7 .
• Takahashi M, Gotoh Y, Isagawa T, etal . Regulation of a mitogen-activated protein kinase kinase kinase, MLTK by PKN. . J. Biochem. . 133 . 2 . 181–7 . 2004 . 12761180 . 10.1093/jb/mvg022 .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Cho YY, Bode AM, Mizuno H, etal . A novel role for mixed-lineage kinase-like mitogen-activated protein triple kinase alpha in neoplastic cell transformation and tumor development. . Cancer Res. . 64 . 11 . 3855–64 . 2004 . 15172994 . 10.1158/0008-5472.CAN-04-0201 . free .
• Jin J, Smith FD, Stark C, etal . Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization. . Curr. Biol. . 14 . 16 . 1436–50 . 2004 . 15324660 . 10.1016/j.cub.2004.07.051 . 2371325 . free .
• Tosti E, Waldbaum L, Warshaw G, etal . The stress kinase MRK contributes to regulation of DNA damage checkpoints through a p38gamma-independent pathway. . J. Biol. Chem. . 279 . 46 . 47652–60 . 2005 . 15342622 . 10.1074/jbc.M409961200 . free .
• Huang CY, Kuo WW, Chueh PJ, etal . Transforming growth factor-beta induces the expression of ANF and hypertrophic growth in cultured cardiomyoblast cells through ZAK. . Biochem. Biophys. Res. Commun. . 324 . 1 . 424–31 . 2004 . 15465036 . 10.1016/j.bbrc.2004.09.067 .
• Huang CY, Chueh PJ, Tseng CT, etal . ZAK re-programs atrial natriuretic factor expression and induces hypertrophic growth in H9c2 cardiomyoblast cells. . Biochem. Biophys. Res. Commun. . 324 . 3 . 973–80 . 2004 . 15485649 . 10.1016/j.bbrc.2004.09.156 .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Choi HS, Choi BY, Cho YY, etal . Phosphorylation of Ser28 in histone H3 mediated by mixed lineage kinase-like mitogen-activated protein triple kinase alpha. . J. Biol. Chem. . 280 . 14 . 13545–53 . 2005 . 15684425 . 10.1074/jbc.M410521200 . free .
• Wang X, Mader MM, Toth JE, etal . Complete inhibition of anisomycin and UV radiation but not cytokine induced JNK and p38 activation by an aryl-substituted dihydropyrrolopyrazole quinoline and mixed lineage kinase 7 small interfering RNA. . J. Biol. Chem. . 280 . 19 . 19298–305 . 2005 . 15737997 . 10.1074/jbc.M413059200 . free .
• Benzinger A, Muster N, Koch HB, etal . Targeted proteomic analysis of 14-3-3 sigma, a p53 effector commonly silenced in cancer. . Mol. Cell. Proteomics . 4 . 6 . 785–95 . 2005 . 15778465 . 10.1074/mcp.M500021-MCP200 . free .
• Hillier LW, Graves TA, Fulton RS, etal . Generation and annotation of the DNA sequences of human chromosomes 2 and 4. . Nature . 434 . 7034 . 724–31 . 2005 . 15815621 . 10.1038/nature03466 . 2005Natur.434..724H . free .
• Rual JF, Venkatesan K, Hao T, etal . Towards a proteome-scale map of the human protein-protein interaction network. . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .

Notes and References

1. Web site: Entrez Gene: ZAK sterile alpha motif and leucine zipper containing kinase AZK.
2. Cloning and Expression of ZAK, a Mixed Lineage Kinase-like Protein Containing a Leucine-Zipper and a Sterile-Alpha Motif . Biochemical and Biophysical Research Communications . 274 . 3 . 11 August 2000 . 811–816 . 10.1006/bbrc.2000.3236. 10924358 . Liu . Te-Chung . Huang . Chang-Jen . Chu . Yu-Chuan . Wei . Chih-Chang . Chou . Chun-Chieh . Chou . Ming-Yung . Chou . Chen-Kung . Yang . Jaw-Ji .
3. 10.1016/S0006-291X(02)02980-7 . Yang . Jaw-Ji . Jan 2003 . A novel zinc finger protein, ZZaPK, interacts with ZAK and stimulates the ZAK-expressing cells re-entering the cell cycle . Biochem. Biophys. Res. Commun. . 301 . 1 . 71–7 . 0006-291X. 12535642 .