生物谷報(bào)道：日前,，芬蘭赫爾辛基大學(xué)領(lǐng)導(dǎo)的一個(gè)研究小組克隆出人類90%以上的功能型蛋白激酶基因和一系列相應(yīng)的缺乏催化活性的激酶，用來進(jìn)行蛋白激酶的功能性研究。
研究人員人類基因組中分離克隆出蛋白激酶基因,，該類基因通過磷酸化和去磷酸化調(diào)控其他蛋白，參與細(xì)胞信號(hào)傳導(dǎo)過程。據(jù)估計(jì)，約1/4的激酶在人類癌癥患病過程中發(fā)生重要作用,。研究小組進(jìn)一步利用他們克隆出的激酶基因組群進(jìn)行了蛋白激酶的高通量篩選，獲得了2個(gè)新的激酶,。一個(gè)起到調(diào)節(jié)“刺猬”信號(hào)通路的作用,，這一通路與多個(gè)類型的人類癌癥密切相關(guān)；另一種新的激酶則與卡波氏肉瘤泡疹病毒的作用相關(guān),。
這項(xiàng)研究分離出的眾多激酶基因?qū)⒆罱K形成一個(gè)基因庫,，可為日后系統(tǒng)分析激酶信號(hào)在不同的細(xì)胞疾病模式中的作用奠定基礎(chǔ)。而且,，激酶同樣可以成為藥物治療的靶標(biāo),，通過了解激酶，人類可以進(jìn)而對(duì)付各種各樣的癌癥,。研究結(jié)果發(fā)表在2號(hào)出版的cell上面,。（生物谷www.bioon.com）
生物谷推薦原始出處：
Cell, Vol 133, 537-548, 02 May 2008
Application of Active and Kinase-Deficient Kinome Collection for Identification of Kinases Regulating Hedgehog Signaling
Markku Varjosalo,1,2,3,8 Mikael Björklund,1,2,3,8 Fang Cheng,2 Heidi Syvänen,1,2,3 Teemu Kivioja,1,2,4 Sami Kilpinen,2,5 Zairen Sun,6 Olli Kallioniemi,2,5 Hendrik G. Stunnenberg,7 Wei-Wu He,6 Päivi Ojala,2, and Jussi Taipale1,2,3,
1 Department of Molecular Medicine, National Public Health Institute (KTL), FI00290 Helsinki, Finland
2 Genome-Scale Biology Program, Biomedicum Helsinki, Institute of Biomedicine, University of Helsinki, PO Box 63, FI-00014, Finland
3 High Throughput Center, University of Helsinki, PO Box 63, FI-00014, Finland
4 Department of Computer Science, University of Helsinki, PO Box 63, FI-00014, Finland
5 Medical Biotechnology Center, VTT Technical Research Centre of Finland and University of Turku, Itäinen Pitkäkatu 4A, FI-20520 Turku, Finland
6 OriGene Technologies Inc, Six Taft Court, Suite 100, Rockville, MD 20850, USA
7 Department of Molecular Biology, Radboud University Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
Summary
To allow genome-scale identification of genes that regulate cellular signaling, we cloned >90% of all human full-length protein kinase cDNAs and constructed the corresponding kinase activity-deficient mutants. To establish the utility of this resource, we tested the effect of expression of the kinases on three different cellular signaling models. In all screens, many kinases had a modest but significant effect, apparently due to crosstalk between signaling pathways. However, the strongest effects were found with known regulators and novel components, such as MAP3K10 and DYRK2, which we identified in a mammalian Hedgehog (Hh) signaling screen. DYRK2 directly phosphorylated and induced the proteasome-dependent degradation of the key Hh pathway-regulated transcription factor, GLI2. MAP3K10, in turn, affected GLI2 indirectly by modulating the activity of DYRK2 and the known Hh pathway component, GSK3β
. Our results establish kinome expression screening as a highly effective way to identify physiological signaling pathway components and genes involved in pathological signaling crosstalk.
