STK4 explained

Serine/threonine-protein kinase 4 is an enzyme that in humans is encoded by the STK4 gene.^{[1] [2] [3]}

Function

The protein encoded by this gene is a cytoplasmic kinase that is structurally similar to the yeast Ste20p (sterile 20 protein) kinase, which acts upstream of the stress-induced mitogen-activated protein kinase (MAPK) cascade. The encoded protein can phosphorylate myelin basic protein and undergoes autophosphorylation. A caspase-cleaved fragment of the encoded protein has been shown to be capable of phosphorylating histone H2B. The particular phosphorylation catalyzed by this protein has been correlated with apoptosis, and it's possible that this protein induces the chromatin condensation observed in this process.^[4]

Interactions

STK4 has been shown to interact with PRKRIR.^[5]

STK4 has also been shown to prevent, through Yap1 coactivator modulation, haematological tumor cell apoptosis.^[6]

Further reading

• Choi J, Oh S, Lee D, Oh HJ, Park JY, Lee SB, Lim DS . Mst1-FoxO signaling protects Naïve T lymphocytes from cellular oxidative stress in mice . PLOS ONE . 4 . 11 . e8011 . 2009 . 19956688 . 2776980 . 10.1371/journal.pone.0008011 . 2009PLoSO...4.8011C . Kaeberlein . Matt . free .
• de Souza PM, Lindsay MA . Mammalian Sterile20-like kinase 1 and the regulation of apoptosis . Biochem. Soc. Trans. . 32 . Pt3 . 485–8 . 2004 . 15157167 . 10.1042/BST0320485 .
• Han S, Stuart LA, Degen SJ . Characterization of the DNF15S2 locus on human chromosome 3: identification of a gene coding for four kringle domains with homology to hepatocyte growth factor . Biochemistry . 30 . 40 . 9768–80 . 1991 . 1655021 . 10.1021/bi00104a029 .
• Gerber MJ, Drabkin HA, Firnhaber C, Miller YE, Scoggin CH, Smith DI . Regional localization of chromosome 3-specific DNA fragments by using a hybrid cell deletion mapping panel . Am. J. Hum. Genet. . 43 . 4 . 442–51 . 1988 . 2902784 . 1715492 .
• Creasy CL, Chernoff J . Cloning and characterization of a human protein kinase with homology to Ste20 . J. Biol. Chem. . 270 . 37 . 21695–700 . 1995 . 7665586 . 10.1074/jbc.270.37.21695 . free .
• Schultz SJ, Nigg EA . Identification of 21 novel human protein kinases, including 3 members of a family related to the cell cycle regulator nimA of Aspergillus nidulans . Cell Growth Differ. . 4 . 10 . 821–30 . 1993 . 8274451 .
• Creasy CL, Chernoff J . Cloning and characterization of a member of the MST subfamily of Ste20-like kinases . Gene . 167 . 1–2 . 303–6 . 1995 . 8566796 . 10.1016/0378-1119(95)00653-2 .
• Creasy CL, Ambrose DM, Chernoff J . The Ste20-like protein kinase, Mst1, dimerizes and contains an inhibitory domain . J. Biol. Chem. . 271 . 35 . 21049–53 . 1996 . 8702870 . 10.1074/jbc.271.35.21049 . free .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Res. . 6 . 9 . 791–806 . 1996 . 8889548 . 10.1101/gr.6.9.791 . free .
• Lee KK, Ohyama T, Yajima N, Tsubuki S, Yonehara S . MST, a physiological caspase substrate, highly sensitizes apoptosis both upstream and downstream of caspase activation . J. Biol. Chem. . 276 . 22 . 19276–85 . 2001 . 11278283 . 10.1074/jbc.M005109200 . free .
• Graves JD, Draves KE, Gotoh Y, Krebs EG, Clark EA . Both phosphorylation and caspase-mediated cleavage contribute to regulation of the Ste20-like protein kinase Mst1 during CD95/Fas-induced apoptosis . J. Biol. Chem. . 276 . 18 . 14909–15 . 2001 . 11278782 . 10.1074/jbc.M010905200 . free .
• Lee KK, Yonehara S . Phosphorylation and dimerization regulate nucleocytoplasmic shuttling of mammalian STE20-like kinase (MST) . J. Biol. Chem. . 277 . 14 . 12351–8 . 2002 . 11805089 . 10.1074/jbc.M108138200 . free .
• Khokhlatchev A, Rabizadeh S, Xavier R, Nedwidek M, Chen T, Zhang XF, Seed B, Avruch J . Identification of a novel Ras-regulated proapoptotic pathway . Curr. Biol. . 12 . 4 . 253–65 . 2002 . 11864565 . 10.1016/S0960-9822(02)00683-8 . 14053233 . free .
• De Souza PM, Kankaanranta H, Michael A, Barnes PJ, Giembycz MA, Lindsay MA . Caspase-catalyzed cleavage and activation of Mst1 correlates with eosinophil but not neutrophil apoptosis . Blood . 99 . 9 . 3432–8 . 2002 . 11964314 . 10.1182/blood.V99.9.3432 . free .
• Glantschnig H, Rodan GA, Reszka AA . Mapping of MST1 kinase sites of phosphorylation. Activation and autophosphorylation . J. Biol. Chem. . 277 . 45 . 42987–96 . 2002 . 12223493 . 10.1074/jbc.M208538200 . free .
• Lin Y, Khokhlatchev A, Figeys D, Avruch J . Death-associated protein 4 binds MST1 and augments MST1-induced apoptosis . J. Biol. Chem. . 277 . 50 . 47991–8001 . 2002 . 12384512 . 10.1074/jbc.M202630200 . free .

Notes and References

1. Taylor LK, Wang HC, Erikson RL . Newly identified stress-responsive protein kinases, Krs-1 and Krs-2 . Proc. Natl. Acad. Sci. U.S.A. . 93 . 19 . 10099–104 . November 1996 . 8816758 . 38343 . 10.1073/pnas.93.19.10099 . 1996PNAS...9310099T . free .
2. Graves JD, Gotoh Y, Draves KE, Ambrose D, Han DK, Wright M, Chernoff J, Clark EA, Krebs EG . Caspase-mediated activation and induction of apoptosis by the mammalian Ste20-like kinase Mst1 . EMBO J. . 17 . 8 . 2224–34 . June 1998 . 9545236 . 1170567 . 10.1093/emboj/17.8.2224 .
3. Ura S, Masuyama N, Graves JD, Gotoh Y . Caspase cleavage of MST1 promotes nuclear translocation and chromatin condensation . Proc. Natl. Acad. Sci. U.S.A. . 98 . 18 . 10148–53 . August 2001 . 11517310 . 56930 . 10.1073/pnas.181161698 . 2001PNAS...9810148U . free .
4. Web site: Entrez Gene: STK4 serine/threonine kinase 4.
5. Lin Y, Khokhlatchev A, Figeys D, Avruch J . Death-associated protein 4 binds MST1 and augments MST1-induced apoptosis . J. Biol. Chem. . 277 . 50 . 47991–8001 . December 2002 . 12384512 . 10.1074/jbc.M202630200 . free .
6. Cottini F, Hideshima T, Xu C, Sattler M, Dori M, Agnelli L, ten Hacken E, Bertilaccio MT, Antonini E, Neri A, Ponzoni M, Marcatti M, Richardson PG, Carrasco R, Kimmelman AC, Wong KK, Caligaris-Cappio F, Blandino G, Kuehl WM, Anderson KC, Tonon G . Rescue of Hippo coactivator YAP1 triggers DNA damage-induced apoptosis in hematological cancers . Nat. Med. . 20 . 6 . 599–606 . 2014 . 24813251 . 10.1038/nm.3562 . 4057660.