4i5p

Structural highlights

Function

PLK2_HUMAN Tumor suppressor serine/threonine-protein kinase involved in synaptic plasticity, centriole duplication and G1/S phase transition. Polo-like kinases act by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates CENPJ, NPM1, RAPGEF2, RASGRF1, SNCA, SIPA1L1 and SYNGAP1. Plays a key role in synaptic plasticity and memory by regulating the Ras and Rap protein signaling: required for overactivity-dependent spine remodeling by phosphorylating the Ras activator RASGRF1 and the Rap inhibitor SIPA1L1 leading to their degradation by the proteasome. Conversely, phosphorylates the Rap activator RAPGEF2 and the Ras inhibitor SYNGAP1, promoting their activity. Also regulates synaptic plasticity independently of kinase activity, via its interaction with NSF that disrupts the interaction between NSF and the GRIA2 subunit of AMPARs, leading to a rapid rundown of AMPAR-mediated current that occludes long term depression. Required for procentriole formation and centriole duplication by phosphorylating CENPJ and NPM1, respectively. Its induction by p53/TP53 suggests that it may participate in the mitotic checkpoint following stress.^{[1] [2] [3] [4]}

See Also

• Serine/threonine protein kinase 3D structures

References

1. ↑ Warnke S, Kemmler S, Hames RS, Tsai HL, Hoffmann-Rohrer U, Fry AM, Hoffmann I. Polo-like kinase-2 is required for centriole duplication in mammalian cells. Curr Biol. 2004 Jul 13;14(13):1200-7. PMID:15242618 doi:10.1016/j.cub.2004.06.059
2. ↑ Cizmecioglu O, Warnke S, Arnold M, Duensing S, Hoffmann I. Plk2 regulated centriole duplication is dependent on its localization to the centrioles and a functional polo-box domain. Cell Cycle. 2008 Nov 15;7(22):3548-55. Epub 2008 Nov 26. PMID:19001868
3. ↑ Chang J, Cizmecioglu O, Hoffmann I, Rhee K. PLK2 phosphorylation is critical for CPAP function in procentriole formation during the centrosome cycle. EMBO J. 2010 Jul 21;29(14):2395-406. doi: 10.1038/emboj.2010.118. Epub 2010 Jun, 8. PMID:20531387 doi:10.1038/emboj.2010.118
4. ↑ Krause A, Hoffmann I. Polo-like kinase 2-dependent phosphorylation of NPM/B23 on serine 4 triggers centriole duplication. PLoS One. 2010 Mar 24;5(3):e9849. doi: 10.1371/journal.pone.0009849. PMID:20352051 doi:10.1371/journal.pone.0009849
5. ↑ Aubele DL, Hom RK, Adler M, Galemmo RA Jr, Bowers S, Truong AP, Pan H, Beroza P, Neitz RJ, Yao N, Lin M, Tonn G, Zhang H, Bova MP, Ren Z, Tam D, Ruslim L, Baker J, Diep L, Fitzgerald K, Hoffman J, Motter R, Fauss D, Tanaka P, Dappen M, Jagodzinski J, Chan W, Konradi AW, Latimer L, Zhu YL, Sham HL, Anderson JP, Bergeron M, Artis DR. Selective and Brain-Permeable Polo-like Kinase-2 (Plk-2) Inhibitors That Reduce alpha-Synuclein Phosphorylation in Rat Brain. ChemMedChem. 2013 Aug;8(8):1295-313. doi: 10.1002/cmdc.201300166. Epub 2013 Jun, 21. PMID:23794260 doi:10.1002/cmdc.201300166