PICK1:一个功能多样的药靶蛋白

被引：8

作者：

宋婀莉

高友鹤

机构：

[1] 中国医学科学院基础医学研究所中国协和医科大学基础医学院,医学分子生物学国家重点实验室,蛋白质组学研究中心,病理生理学系

来源：

中国生物化学与分子生物学报 | 2007年 / 09期

基金：

北京市自然科学基金;

关键词：

PICK1(protein interacting with Cαkinase 1); PDZ结构域; 药物靶点; 阻断性多肽;

D O I：

10.13865/j.cnki.cjbmb.2007.09.008

中图分类号：

Q51 [蛋白质];

学科分类号：

070307 [化学生物学];

摘要：

蛋白质是生命功能的执行者.生命体中某些关键蛋白的功能异常往往是导致疾病发生的根本原因.这些疾病相关蛋白极有可能成为药物靶点,为新药研发和疾病治疗提供重要线索.PICK1蛋白(protein interacting with Cαkinase1)结合能力广泛、功能多样以及在多种重要疾病(如:癌症、精神分裂症、疼痛、帕金森综合症等)的发生发展过程中发挥潜在的作用,使其成为一个可能的药靶蛋白.PICK1与绝大多数配体蛋白的相互作用是通过其PDZ结构域与配体C末端区域的结合介导的,使PICK1的PDZ结构域成为一个潜在的药物靶点.因此,可以利用生物小分子物质特异性地结合PICK1的PDZ结构域,干扰或阻断PICK1与配体蛋白的天然相互作用,最终达到治疗相关疾病的目的.

引用

页码：697 / 705

页数：9

共 16 条

[1]

Intracellullar peptides as putative natural regulators of protein interactions [J].

Ferro, ES ;

Hyslop, S ;

Camargo, ACM .

JOURNAL OF NEUROCHEMISTRY, 2004, 91 (04) :769-777

[2]

The complexity of PDZ domain-mediated interactions at glutamatergic synapses: a case study on neuroligin [J].

Meyer, G ;

Varoqueaux, F ;

Neeb, A ;

Oschlies, M ;

Brose, N .

NEUROPHARMACOLOGY, 2004, 47 (05) :724-733

[3]

Interaction between the internal motif KTXXXI of Idax and mDvl PDZ domain [J].

London, TBC ;

Lee, HJ ;

Shao, YM ;

Zheng, J .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2004, 322 (01) :326-332

[4]

Brain-derived neurotrophic factor signal enhances and maintains the expression of AMPA receptor-associated PDZ proteins in developing cortical neurons [J].

Jourdi, H ;

Iwakura, Y ;

Narisawa-Saito, M ;

Ibaraki, K ;

Xiong, HB ;

Watanabe, M ;

Hayashi, Y ;

Takei, N ;

Nawa, H .

DEVELOPMENTAL BIOLOGY, 2003, 263 (02) :216-230

[5]

Rapid induction of dendritic spine morphogenesis by trans-synaptic EphrinB-EphB receptor activation of the Rho-GEF kalirin [J].

Penzes, P ;

Beeser, A ;

Chernoff, J ;

Schiller, MR ;

Eipper, BA ;

Mains, RE ;

Huganir, RL .

NEURON, 2003, 37 (02) :263-274

[6]

Rapid and differential regulation of AMPA and kainate receptors at hippocampal mossy fibre Synapses by PICK1 and GRIP [J].

Hirbec, H ;

Francis, JC ;

Lauri, SE ;

Braithwaite, SP ;

Coussen, F ;

Mulle, C ;

Dev, KK ;

Couthino, V ;

Meyer, G ;

Isaac, JTR ;

Collingridge, GL ;

Henley, JM .

NEURON, 2003, 37 (04) :625-638

[7]

A PDZ domain-based detection system for enzymatic assays [J].

Ferrer, M ;

Hamilton, AC ;

Inglese, J .

ANALYTICAL BIOCHEMISTRY, 2002, 301 (02) :207-216

[8]

Gene transfer into neurons from hippocampal slices:: Comparison of recombinant Semliki Forest virus, adenovirus, adeno-associated virus, lentivirus, and measles virus [J].

Ehrengruber, MU ;

Hennou, S ;

Büeler, H ;

Naim, HY ;

Déglon, N ;

Lundstrom, K .

MOLECULAR AND CELLULAR NEUROSCIENCE, 2001, 17 (05) :855-871

[9]

Functional Interaction between Monoamine Plasma Membrane Transporters and the Synaptic PDZ Domain–Containing Protein PICK1.[J].Gonzalo E Torres;Wei-Dong Yao;Amy R Mohn;Hui Quan;Kyeong-Man Kim;Allan I Levey;Jeff Staudinger;Marc G Caron.Neuron.2001, 1

[10]

Interaction of the PDZ domain of human PICK1 with class I ADP-ribosylation factors [J].

Takeya, R ;

Takeshige, K ;

Sumimoto, H .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 267 (01) :149-155

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