LYK5 explained

Protein kinase LYK5, also known as LYK5 or STRADα, is a human protein and also denotes the gene encoding it.^{[1] [2]}

Function

Endogenous LKB1 and STRADα form a complex in which STRADα activates LKB1, resulting in phosphorylation of both partners. Removal of endogenous LYK5 by small interfering RNA abrogates LKB1-induced G1 phase arrest.^[2] STRADα stabilizes LKB1 protein both in vivo and in vitro, and is capable of eliciting multiple axons in mouse embryonic cortical cultured neurons when overexpressed with LKB1. STRADα is highly spliced in vivo,^[3] and this is both developmentally regulated and tissue-specific, but the unique functions of the splice variants are not yet understood.^[4]

Disease linkage

Mutations in the LYK5/STRADα gene are associated with polyhydramnios, megalencephaly and symptomatic epilepsy (collectively known as the PMSE syndrome).^[5]

Interactions

STRADα has been shown to interact with LKB1 and MO25.^[6]

Further reading

• Baas AF, Smit L, Clevers H . LKB1 tumor suppressor protein: PARtaker in cell polarity. . Trends Cell Biol. . 14 . 6 . 312–9 . 2004 . 15183188 . 10.1016/j.tcb.2004.04.001 .
• Scanlan MJ, Gout I, Gordon CM, Williamson B, Stockert E, Gure AO, Jäger D, Chen YT, Mackay A, O'Hare MJ, Old LJ . Humoral immunity to human breast cancer: antigen definition and quantitative analysis of mRNA expression. . Cancer Immun. . 1 . 4 . 2003 . 12747765 .
• Baas AF, Boudeau J, Sapkota GP, Smit L, Medema R, Morrice NA, Alessi DR, Clevers HC . Activation of the tumour suppressor kinase LKB1 by the STE20-like pseudokinase STRAD. . EMBO J. . 22 . 12 . 3062–72 . 2003 . 12805220 . 162144 . 10.1093/emboj/cdg292 .
• Boudeau J, Baas AF, Deak M, Morrice NA, Kieloch A, Schutkowski M, Prescott AR, Clevers HC, Alessi DR . MO25alpha/beta interact with STRADalpha/beta enhancing their ability to bind, activate and localize LKB1 in the cytoplasm. . EMBO J. . 22 . 19 . 5102–14 . 2003 . 14517248 . 204473 . 10.1093/emboj/cdg490 .
• Milburn CC, Boudeau J, Deak M, Alessi DR, van Aalten DM . Crystal structure of MO25 alpha in complex with the C terminus of the pseudo kinase STE20-related adaptor. . Nat. Struct. Mol. Biol. . 11 . 2 . 193–200 . 2004 . 14730349 . 10.1038/nsmb716 . 18401688 .
• Lizcano JM, Göransson O, Toth R, Deak M, Morrice NA, Boudeau J, Hawley SA, Udd L, Mäkelä TP, Hardie DG, Alessi DR . LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1. . EMBO J. . 23 . 4 . 833–43 . 2005 . 14976552 . 381014 . 10.1038/sj.emboj.7600110 .
• Boudeau J, Scott JW, Resta N, Deak M, Kieloch A, Komander D, Hardie DG, Prescott AR, van Aalten DM, Alessi DR . Analysis of the LKB1-STRAD-MO25 complex. . J. Cell Sci. . 117 . Pt 26 . 6365–75 . 2005 . 15561763 . 10.1242/jcs.01571 . free .
• Veleva-Rotse BO, Smart JL, Baas AF, Edmonds B, Zhao ZM, Brown A, Klug LR, Hansen K, Reilly G, Gardner AP, Subbiah K, Gaucher EA, Clevers H, Barnes AP . STRAD pseudokinases regulate axogenesis and LKB1 stability. . Neural Dev . 9 . 5 . 2014 . 5 . 24594058 . 10.1186/1749-8104-9-5 . 4016016 . free .

Notes and References

1. Web site: Entrez Gene: LYK5 protein kinase LYK5.
2. Baas AF, Boudeau J, Sapkota GP, Smit L, Medema R, Morrice NA, Alessi DR, Clevers HC . Activation of the tumour suppressor kinase LKB1 by the STE20-like pseudokinase STRAD . EMBO J. . 22 . 12 . 3062–72 . June 2003 . 12805220 . 162144 . 10.1093/emboj/cdg292 .
3. Marignani . Paola A. . Scott . Kristine . Bagnulo . Rosanna . Cannone . Domenico . Ferrari . Eleonora . Stella . Alessandro . Guanti . Ginevra . Simone . Cristiano . Resta . Nicoletta . October 2007 . Novel splice isoforms of STRADα differentially affect LKB1 activity, complex assembly and subcellular localization. . Cancer Biology & Therapy . en . 6 . 10 . 1627–1631 . 10.4161/cbt.6.10.4787 . 17921699 . 1538-4047.
4. Veleva-Rotse BO, Smart JL, Baas AF, Edmonds B, Zhao ZM, Brown A, Klug LR, Hansen K, Reilly G, Gardner AP, Subbiah K, Gaucher EA, Clevers H, Barnes AP . STRAD pseudokinases regulate axogenesis and LKB1 stability. . Neural Dev . 9 . 5 . 2014 . 5 . 24594058 . 10.1186/1749-8104-9-5 . 4016016 . free . /
5. Puffenberger EG, Strauss KA, Ramsey KE, Craig DW, Stephan DA, Robinson DL, Hendrickson CL, Gottlieb S, Ramsay DA, Siu VM, Heuer GG, Crino PB, Morton DH . Polyhydramnios, megalencephaly and symptomatic epilepsy caused by a homozygous 7-kilobase deletion in LYK5 . Brain . 130 . Pt 7 . 1929–41 . July 2007 . 17522105 . 10.1093/brain/awm100 . free .
6. Boudeau J, Scott JW, Resta N, Deak M, Kieloch A, Komander D, Hardie DG, Prescott AR, van Aalten DM, Alessi DR . Analysis of the LKB1-STRAD-MO25 complex . J. Cell Sci. . 117 . Pt 26 . 6365–75 . Dec 2004 . 15561763 . 10.1242/jcs.01571 . free .