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    Title: 蛋白激脢之細胞訊息傳遞路徑中DARPP-32蛋白所扮演的角色---對大鼠學習記憶和抗細胞凋亡機制的影響
    Other Titles: Role and Mechanism of DARPP-32 in Protein Kinase CK2-Mediated Signaling Pathway---Influence on Learning &Amp;Memory and Anti-Apoptosis
    Authors: 趙知章
    Contributors: 國立政治大學神經科學研究所
    行政院國家科學委員會
    Keywords: 基礎醫學;生物技術;蛋白激脢;細胞訊息傳遞路徑;DARPP-32蛋白;大鼠;學習記憶;抗細胞凋亡
    Date: 2010
    Issue Date: 2012-11-15 11:23:47 (UTC+8)
    Abstract: 蛋白激&;#37238; CK2是屬於一種serine/threonine &;#63952;的蛋白激&;#37238;,CK2 與抗細胞凋亡相關的議題已被廣泛探討,這些研究報告指出CK2可以經由活化Akt/PKB、NF-kB 和ARC 蛋白(apoptosis repressor with caspase recruitment domain)等機制&;#63789;促進細胞的存活。蛋白dopamine and cyclic AMP-regulated phosphoprotein, Mr. 32kDa(DARPP-32)最初是在紋&;#63994;體腦區中被發現的,主要受到&;#63789;自多巴胺的&;#63999;激增加&;#63930;細胞內cAMP的含&;#63870;進而活化Protein kinase A對DARPP-32蛋白進&;#64008;磷酸化作用,近&;#63886;&;#63789;的研究指出DARPP-32 除&;#63930;與藥物成癮的生&;#63972;現象有關外,應該還&;#63851;與在其他生&;#63972;調控或改變的機制之中,諸如:DARPP-32和其isoform tDARPP 也在腸胃癌細胞內被發現有較高的表現&;#63870;而且可以減緩癌細胞的死亡,因此DARPP-32也有&;#63851;與在抗細胞凋亡機制之中的可能性。由於DARPP-32 Ser102是CK2磷酸化作用的位置,我們最近的研究發現CK2&;#63851;與在BDNF抗細胞凋亡的機制之中,承續此研究結果,本研究計畫今&;#63886;&;#64001;的研究利用委託合成的DARPP-32 Ser102磷酸化抗體的相關初步實驗結果顯示,轉染野生型的CK2-WT的DNA質體確實會增加細胞內DARPP-32 Ser102胺基酸的磷酸化現象,並且也會顯著增加 Bcl-xL蛋白質的表現;轉染DARPP-32 Ser102A的DNA質體可觀察到細胞內Bcl-xL蛋白質的表現量有顯著減少的變化,初步驗證了抗細胞凋亡蛋白Bcl-x pre-mRNA的alternative splicing與蛋白激&;#37238;CK2 對DARPP-32 S102胺基酸的磷酸化作用之間存在有相關性。
    Protein kinase CK2 is a multifunctional and ubiquitous serine/threonine protein kinase. Many studies of CK2 are focused on its anti-apoptotic effects. There are many reports showing that CK2 could activate protein kinase Akt, NF-B and ARC protein (apoptosis repressor with caspase recruitment domain) and to enhance cell survival. Meanwhile, the dopamine and cyclic AMP-regulated phosphoprotein, Mr. 32kDa (DARPP-32) was originally found to be activated by dopamine and cAMP through PKA-dependent phosphorylation in the striatum. Beside it well-known role in drug addiction, recent studies indicated that DARPP-32 might also involve in other physiological functions. The higher protein expression of DARPP-32 and its isoform tDARPP were found in the gastrointestinal carcinomas and were relative to maintain the cell survival. The DARPP-32 Ser102 have been identified to be phosphorylated by Ck2. In our previous study, we found that CK2 activation was involved in the anti-apoptotic effects of BDNF. In the present study, we found that transfection of CK2-WT DNA plasmid increases the phosphorylation level of DARPP-32 Ser102 and the protein level of Bcl-xL. Further study also found that transfection of mutant DARPP-32 S102A DNA plasmid decreases the protein level of Bcl-xL. The detailed cellular mechanism are under investigation..
    Relation: 基礎研究
    學術補助
    研究期間:9908~ 10007
    研究經費: 1100仟元
    Data Type: report
    Appears in Collections:[神經科學研究所] 國科會研究計畫

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