Promotion of Pink1S Auto-phosphorylation with CK2β_Journal of Biomedical Engineering

Authors：

QINSiyue , JIANGChangan

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China 2^nd University Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

Keywords：

Parkinson's disease; PINK1S; CK2β; auto-phosphorylation

DOI：

10.7507/1001-5515.20150187

Video：

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The aim of this study is to determine the regulatory mechanism of PTEN-induced putative kinase protein 1 short isoform (PINK1S) in cytoplasm. By co-immunoprecipitation (Co-IP) assay, we identified that PINK1S interacted with the beta regulatory subunit of Casein Kinase 2 (CK2β), but not with the catalytic subunits CK2α1 and CK2α2. Furthermore, cells were transfected with PINK1S and CK2β, and then PINK1S was purified by immunoprecipitation. After detecting the phosphorylated proteins by Phos-tag^TM Biotin, we found that CK2β overexpression increased auto-phosphorylation of PINK1S. Finally, we generated CK2β knockdown cell lines by RNA interference. Purified PINK1S from CK2β knockdown cells significantly reduced its auto-phosphorylation compared with control cells. These results suggested that CK2β functions as a regulatory subunit of PINK1S kinase complex promoted its activation by self-phosphorylation.

Citation： QINSiyue, JIANGChangan. Promotion of Pink1S Auto-phosphorylation with CK2β. Journal of Biomedical Engineering, 2015, 32(5): 1056-1060. doi: 10.7507/1001-5515.20150187 Copy

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7.	FILHOL, MARTIEL J L and COCHET C. Protein kinase CK2:a new view of an old molecular complex[J]. EMBO Rep, 2004, 5(4):351-355.
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11.	SIUDA J, JASINSKA-MYGA B, BOCZARSKA-JEDYNAK M, et al. Early-onset Parkinson's disease due to PINK1 p.Q456X mutation-Clinical and functional study[J]. Parkinsonism Relat Disord, 2014, pii:S1353-8020(14)00317-4.
12.	KOZLOV S V, GRAHAM M E, JAKOB B, et al. Autophosphorylation and ATM activation:additional sites add to the complexity[J]. J Biol Chem, 2011, 286(11):9107-9119.
13.	LIU S, SHIOTANI B, LAHIRI M, et al. ATR autophosphorylation as a molecular switch for checkpoint activation[J]. Mol Cell, 2011, 43(2):192-202.
14.	TRUJILLO R, MIRO F, PLANA M, et al. Substrates for protein kinase CK2 in insulin receptor preparations from rat liver membranes:identification of a 210-kDa protein substrate as the dimeric form of endoplasmin[J]. Arch Biochem Biophys, 1997, 344(1):18-28.
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1. GRAUL A I and KAMERKAR S. Parkinson's disease in the limelight[J]. Drugs Today (Barc), 2014, 50(9):641-645.
2. VALENTE E M, ABOU-SLEIMAN P M, Caputo V, et al. Hereditary early-onset Parkinson's disease caused by mutations in PINK1[J]. Science, 2004, 304(5674):1158-1160.
3. VIVES-BAUZA C, ZHOU C, HUANG Y, et al. PINK1-dependent recruitment of Parkin to mitochondria in mitophagy[J]. Proc Natl Acad Sci U S A, 2010, 107(1):378-383.
4. YAMANO K and YOULE R J. PINK1 is degraded through the N-end rule pathway[J]. Autophagy, 2013, 9(11):1758-1769.
5. OKATSU K, OKA T, IGUCHI M, et al. PINK1 autophosphorylation upon membrane potential dissipation is essential for Parkin recruitment to damaged mitochondria[J]. Nat Commun, 2012, 3:1016.
6. BIBBY A C and LITCHFIELD D W. The multiple personalities of the regulatory subunit of protein kinase CK2:CK2 dependent and CK2 independent roles reveal a secret identity for CK2beta[J]. Int J Biol Sci, 2005, 1(2):67-79.
7. FILHOL, MARTIEL J L and COCHET C. Protein kinase CK2:a new view of an old molecular complex[J]. EMBO Rep, 2004, 5(4):351-355.
8. YDE C W, OLSEN B B, MEEK D, et al. The regulatory beta-subunit of protein kinase CK2 regulates cell-cycle progression at the onset of mitosis[J]. Oncogene, 2008, 27(37):4986-4997.
9. TANG B, XIONG H, SUN P, et al. Association of PINK1 and DJ-1 confers digenic inheritance of early-onset Parkinson's disease[J]. Hum Mol Genet, 2006, 15(11):1816-1825.
10. TOFT M, MYHRE R, PIELSTICKER L, et al. PINK1 mutation heterozygosity and the risk of Parkinson's disease[J]. J Neurol Neurosurg Psychiatry, 2007, 78(1):82-84.
11. SIUDA J, JASINSKA-MYGA B, BOCZARSKA-JEDYNAK M, et al. Early-onset Parkinson's disease due to PINK1 p.Q456X mutation-Clinical and functional study[J]. Parkinsonism Relat Disord, 2014, pii:S1353-8020(14)00317-4.
12. KOZLOV S V, GRAHAM M E, JAKOB B, et al. Autophosphorylation and ATM activation:additional sites add to the complexity[J]. J Biol Chem, 2011, 286(11):9107-9119.
13. LIU S, SHIOTANI B, LAHIRI M, et al. ATR autophosphorylation as a molecular switch for checkpoint activation[J]. Mol Cell, 2011, 43(2):192-202.
14. TRUJILLO R, MIRO F, PLANA M, et al. Substrates for protein kinase CK2 in insulin receptor preparations from rat liver membranes:identification of a 210-kDa protein substrate as the dimeric form of endoplasmin[J]. Arch Biochem Biophys, 1997, 344(1):18-28.
15. SARNO S, VAGLIO P, MEGGIO F, et al. Protein kinase CK2 mutants defective in substrate recognition. Purification and kinetic analysis[J]. J Biol Chem, 1996, 271(18):10595-10601.

Journal of Biomedical Engineering

Promotion of Pink1S Auto-phosphorylation with CK2β

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