LYK5
Protein kinase LYK5, also known as LYK5 or STRADα, is a human protein and also denotes the gene encoding it.[5][6]
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.[6] 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, and this is both developmentally regulated and tissue-specific, but the unique functions of the splice variants are not yet understood.[7]
Disease linkage
Mutations in the LYK5/STRADα gene are associated with polyhydramnios, megalencephaly and symptomatic epilepsy (collectively known as the PMSE syndrome).[8]
References
- GRCh38: Ensembl release 89: ENSG00000266173 - Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000069631 - Ensembl, May 2017
- "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Entrez Gene: LYK5 protein kinase LYK5".
- Baas AF, Boudeau J, Sapkota GP, Smit L, Medema R, Morrice NA, Alessi DR, Clevers HC (June 2003). "Activation of the tumour suppressor kinase LKB1 by the STE20-like pseudokinase STRAD". EMBO J. 22 (12): 3062–72. doi:10.1093/emboj/cdg292. PMC 162144. PMID 12805220.
- 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 (2014). "STRAD pseudokinases regulate axogenesis and LKB1 stability". Neural Dev. 9 (5): 5. doi:10.1186/1749-8104-9-5. PMC 4016016. PMID 24594058./
- 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 (July 2007). "Polyhydramnios, megalencephaly and symptomatic epilepsy caused by a homozygous 7-kilobase deletion in LYK5". Brain. 130 (Pt 7): 1929–41. doi:10.1093/brain/awm100. PMID 17522105.
- Boudeau J, Scott JW, Resta N, Deak M, Kieloch A, Komander D, Hardie DG, Prescott AR, van Aalten DM, Alessi DR (Dec 2004). "Analysis of the LKB1-STRAD-MO25 complex". J. Cell Sci. 117 (Pt 26): 6365–75. doi:10.1242/jcs.01571. PMID 15561763.
Further reading
- Baas AF, Smit L, Clevers H (2004). "LKB1 tumor suppressor protein: PARtaker in cell polarity". Trends Cell Biol. 14 (6): 312–9. doi:10.1016/j.tcb.2004.04.001. PMID 15183188.
- Scanlan MJ, Gout I, Gordon CM, Williamson B, Stockert E, Gure AO, Jäger D, Chen YT, Mackay A, O'Hare MJ, Old LJ (2003). "Humoral immunity to human breast cancer: antigen definition and quantitative analysis of mRNA expression". Cancer Immun. 1: 4. PMID 12747765.
- Baas AF, Boudeau J, Sapkota GP, Smit L, Medema R, Morrice NA, Alessi DR, Clevers HC (2003). "Activation of the tumour suppressor kinase LKB1 by the STE20-like pseudokinase STRAD". EMBO J. 22 (12): 3062–72. doi:10.1093/emboj/cdg292. PMC 162144. PMID 12805220.
- Boudeau J, Baas AF, Deak M, Morrice NA, Kieloch A, Schutkowski M, Prescott AR, Clevers HC, Alessi DR (2003). "MO25alpha/beta interact with STRADalpha/beta enhancing their ability to bind, activate and localize LKB1 in the cytoplasm". EMBO J. 22 (19): 5102–14. doi:10.1093/emboj/cdg490. PMC 204473. PMID 14517248.
- Milburn CC, Boudeau J, Deak M, Alessi DR, van Aalten DM (2004). "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. doi:10.1038/nsmb716. PMID 14730349. S2CID 18401688.
- Lizcano JM, Göransson O, Toth R, Deak M, Morrice NA, Boudeau J, Hawley SA, Udd L, Mäkelä TP, Hardie DG, Alessi DR (2005). "LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1". EMBO J. 23 (4): 833–43. doi:10.1038/sj.emboj.7600110. PMC 381014. PMID 14976552.
- Boudeau J, Scott JW, Resta N, Deak M, Kieloch A, Komander D, Hardie DG, Prescott AR, van Aalten DM, Alessi DR (2005). "Analysis of the LKB1-STRAD-MO25 complex". J. Cell Sci. 117 (Pt 26): 6365–75. doi:10.1242/jcs.01571. PMID 15561763.
- 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 (2014). "STRAD pseudokinases regulate axogenesis and LKB1 stability". Neural Dev. 9 (5): 5. doi:10.1186/1749-8104-9-5. PMC 4016016. PMID 24594058.
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