近日，英国皇家学会《开放生物学》（Open Biology）杂志发表帕金森症研究新发现，该成果向发现帕金森症病因又迈进了一步。
英国帕金森症患者近12万人，病因研究方面始终未获突破进展，目前仍没有治疗方法。虽然科学家已发现为PINK1蛋白合成指定密码的某个基因的突变导致了帕金森症，但仍不清楚该基因突变是如何引起病变的。
此次研究的突破在于科学家首次发现了测量PINK1活动的方法。科学家发现病变导致PINK1不能正常工作，而PINK1的功能对于神经原的存活十分重要，由此可进一步锁定发现帕金森症病因的新目标。(生物谷 Bioon.com)
doi:10.1016/10.1098/rsob.110012
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Discovery of catalytically active orthologues of the Parkinson's disease kinase PINK1: analysis of substrate specificity and impact of mutations
Helen I. Woodroof,, Joe H. Pogson, Mike Begley, Lewis C. Cantley, Maria Deak, David G. Campbell, Daan M. F. van Aalten, Alexander J. Whitworth, Dario R. Alessi and Miratul M. K. Muqit
Missense mutations of the phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1) gene cause autosomal-recessive Parkinson's disease. To date, little is known about the intrinsic catalytic properties of PINK1 since the human enzyme displays such low kinase activity in vitro. We have discovered that, in contrast to mammalian PINK1, insect orthologues of PINK1 we have investigated—namely Drosophila melanogaster (dPINK1), Tribolium castaneum (TcPINK1) and Pediculus humanus corporis (PhcPINK1)—are active as judged by their ability to phosphorylate the generic substrate myelin basic protein. We have exploited the most active orthologue, TcPINK1, to assess its substrate specificity and elaborated a peptide substrate (PINKtide, KKWIpYRRSPRRR) that can be employed to quantify PINK1 kinase activity. Analysis of PINKtide variants reveal that PINK1 phosphorylates serine or threonine, but not tyrosine, and we show that PINK1 exhibits a preference for a proline at the +1 position relative to the phosphorylation site. We have also, for the first time, been able to investigate the effect of Parkinson's disease-associated PINK1 missense mutations, and found that nearly all those located within the kinase domain, as well as the C-terminal non-catalytic region, markedly suppress kinase activity. This emphasizes the crucial importance of PINK1 kinase activity in preventing the development of Parkinson's disease. Our findings will aid future studies aimed at understanding how the activity of PINK1 is regulated and the identification of physiological substrates.
