耶鲁大学科学家Michael Snyder等首次通过研究酵母中的蛋白磷酸化网络，描绘出控制高等生物的细胞功能的蛋白激酶的信号网络。研究人员指出本研究是一项重大的突破，解释了蛋白激酶这一调控因子如何使蛋白质在不同类型的细胞中发挥作用。尽管目前蛋白激酶已经作为一种重要抗癌药物的靶位点，然而到目前为止受激酶调控的蛋白质还很难确定。
由细胞分子生物学家Michael Snyder负责的研究小组观察了酵母细胞不同蛋白质的表达、相互作用以及细胞中的活性蛋白成分。作为调控因子的蛋白激酶通过对靶蛋白的磷酸化从而使其发挥作用。这一过程最终会导致蛋白质的活性发生改变。据估计，约30％的蛋白质都通过这一途径进行调控。
生物谷认为，采用酵母作为大规模蛋白质间相互作用，或激酶网络模型是近年来研究趋势，先前有报道：酵母膜表面蛋白相互作用的大规模研究、利用RNAi技术对生命活动中的激酶进行大规模研究以及酵母的大规模功能蛋白学研究结果等，这些大规模研究有助于了解生命现象的复杂过程，也有助于理解生命的活动的本质特征。
这项研究结果发表在最近一期的《自然》杂志上。
a, Overall scheme to identify kinase substrates. Each kinase was overexpressed, purified and assayed on protein chips containing about 4,400 proteins spotted in duplicate. b, Kinase assays on protein chips. Two protein chips were used for every kinase assayed. In addition, two protein chips were probed in the absence of kinase to identify proteins on the chip that autophosphorylate. Commercial kinases were spotted at many defined locations, shown in the four corners of the two boxes on the right; these kinases autophosphorylated in our assay and served as landmarks for the identification of phosphorylation signals. The slide on the left is a representative slide probed with anti-GST antibodies indicating the amount of fusion protein present on the proteome slide. c, In vivo validation of targets identified on the proteome microarray: ARK1 (i), SWE1 (ii), HSL1 (iii), BCK1 (iv), STE20 (v) and PRK1 (vi) were deleted from the TAP-tagged strains indicated. From the kinase-deleted strains, the tagged proteins were purified and their phosphorylation status compared with wild-type tagged proteins. Immunoblots were probed with anti-phosphothreonine antibody (i, top panel), anti-phosphotyrosine antibody (ii, top panel) or anti-phosphoserine antibody (iv, top panel). In addition, protein isoforms and protein levels were monitored with anti-CBP antibody (i–vi).
a, A map showing the connections between kinases and substrates. In all, 87 different kinases (red dots) and 1,325 substrates (blue dots) are represented in the map. b, Global localization data can be used to identify only those phosphorylation events occurring between proteins of the same cellular compartment. c, Functional data can be used to identify substrates with similar functions to those of the kinases phosphorylating them.
相关研究报道
·《Nature》：大规模绘制基因图谱的新方法
·《任小二快报》：人类基因组的大规模拷贝数的多态性
·大规模RNAi技术首次在哺乳动物中应用
·中心粒粘附的相关基因的大规模筛选
·用RNAi技术大规模研究基因功能
·酵母的大规模功能蛋白学研究结果
·酵母膜表面蛋白相互作用的大规模研究
·利用RNAi技术对生命活动中的激酶进行大规模研究
·酵母的大规模功能蛋白学研究结果
原始出处：
Jason Ptacek, Geeta Devgan, Gregory Michaud, Heng Zhu, Xiaowei Zhu, Joseph Fasolo, Hong Guo, Ghil Jona, Ashton Breitkreutz, Richelle Sopko, Rhonda R. McCartney, Martin C. Schmidt, Najma Rachidi, Soo-Jung Lee, Angie S. Mah, Lihao Meng, Michael J. R. Stark, David F. Stern, Claudio De Virgilio, Mike Tyers, Brenda Andrews, Mark Gerstein, Barry Schweitzer, Paul F. Predki and Michael Snyder. Global analysis of protein phosphorylation in yeast. Nature 438, 679-684 (1 December 2005)
实验室主页：
Michael Snyder, Ph.D. michael.snyder@yale.edu
Professor and Chairman of Molecular, Cellular, and Developmental Biology;
Professor of Molecular Biophysics & Biochemistry
Contact and Mailing Information
B.A. Chemistry and Biology;
University of Rochester, N.Y. 1977;
Ph.D. Biology California Institute
of Technology 1983;
Helen Hay Whitney Fellow;
Stanford University 1982-86;
Joined Yale Faculty 1986;
United Scleroderma Foundation Award;
Pew Scholar Award 1987-91.
Research Interests:
Molecular Genetics/Cell Biology
