人體內(nèi)每個細胞的運作都受控于訊息網(wǎng)(signaling networks),，外來的刺激物由細胞表面的蛋白質(zhì)接受器(receptor)接收，然后命令細胞分裂或移動等,。西奈山(Mount Sinai)醫(yī)院Samuel Lunenfeld研究院的James Dennis博士發(fā)現(xiàn)醣蛋白上醣類的新角色,，此開創(chuàng)性的研究發(fā)表于頂尖期刊Cell。
人體細胞內(nèi)有許多重要的蛋白質(zhì)在轉(zhuǎn)譯完成后會由一群復雜的醣類裝飾著,，研究人員非常明白,，當這些醣類的種類因遺傳突變或其它變因而被改變時，常與疾病的生成習習相關,，例如：癌癥,、糖尿病或是一些自體免疫疾病，如多發(fā)性硬化癥等,。
目前新一代的抗癌新藥,，Herceptin（一種抗體）就是以此類目標蛋白作為標靶，來對抗位于乳癌細胞上一種叫做Her-2/neu(或稱Erb B-2)的抗原,。因Herceptin (商品名Trastuzumab)獨特之抗癌療效及機轉(zhuǎn),，已于1998年九月底經(jīng)美國藥物食品管理局(FDA)核準上市。Dennis研究團隊目前仍持續(xù)在研究這些重要的醣蛋白,，如荷爾蒙或生長因子,，以觀察這些蛋白質(zhì)上醣鏈分子改變對疾病所造成的影響。而此研究發(fā)現(xiàn)也將促使更多新型抗癌藥物的研發(fā),。
(資料來源 : Bio.com)
原始出處: http://www.bio.com/newsfeatures/newsfeatures_research.jhtml?cid=28100017
部分英文原文：
Cell, Vol 129, 123-134, 06 April 2007
Article
Complex N-Glycan Number and Degree of Branching Cooperate to Regulate Cell Proliferation and Differentiation
Ken S. Lau,1,2 Emily A. Partridge,1,3 Ani Grigorian,4 Cristina I. Silvescu,6 Vernon N. Reinhold,6 Michael Demetriou,4,5 and James W. Dennis1,3,
1 Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue R988, Toronto, ON M5G 1X5, Canada
2 Department of Biochemistry, University of Toronto, ON M5S 1A8, Canada
3 Departments of Molecular & Medical Genetics, Laboratory Medicine and Pathology, University of Toronto, ON M5G 1L5, Canada
4 Department of Microbiology and Molecular Genetics, University of California, Irvine, CA 92697-4025, USA
5 Department of Neurology, University of California, Irvine, CA 92862-4280, USA
6 Chemistry, University of New Hampshire, Durham, NH 03824, USA
Corresponding author
James W. Dennis
[email protected]
The number of N-glycans (n) is a distinct feature of each glycoprotein sequence and cooperates with the physical properties of the Golgi N-glycan-branching pathway to regulate surface glycoprotein levels. The Golgi pathway is ultrasensitive to hexosamine flux for the production of tri- and tetra-antennary N-glycans, which bind to galectins and form a molecular lattice that opposes glycoprotein endocytosis. Glycoproteins with few N-glycans (e.g., TβR, CTLA-4, and GLUT4) exhibit enhanced cell-surface expression with switch-like responses to increasing hexosamine concentration, whereas glycoproteins with high numbers of N-glycans (e.g., EGFR, IGFR, FGFR, and PDGFR) exhibit hyperbolic responses. Computational and experimental data reveal that these features allow nutrient flux stimulated by growth-promoting high-n receptors to drive arrest/differentiation programs by increasing surface levels of low-n glycoproteins. We have identified a mechanism for metabolic regulation of cellular transition between growth and arrest in mammals arising from apparent coevolution of N-glycan number and branching.
