Glycogen Synthase Kinase 3β Interaction Protein Functions as an A-kinase Anchoring Protein
Glycogen Synthase Kinase 3β Interaction Protein Functions as an A-kinase Anchoring Protein
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DOI：
10.1074/jbc.m109.047944
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发表时间：
2010-02-19
影响因子：
4.8
通讯作者：
Klussmann, Enno
中科院分区：
文献类型：
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作者：
Hundsrucker, Christian;Skroblin, Philipp;Klussmann, Enno
A-激酶锚定蛋白(AKAPs)是一类以蛋白激酶A(PKA)和其他信号蛋白为靶点的支架蛋白家族，可将相关蛋白的活性限制在细胞内的不同区域。AKAP直接与PKA结合。这种相互作用是由PKA调节亚基的二聚化和对接结构域以及AKAP的PKA结合结构域介导的。对二聚化和对接结构域与各种PKA结合结构域之间的相互作用进行了分析，得到了一个通用的基序，从而能够鉴定AKAP。我们的生物信息学和基于这个特征基序的多肽阵列筛选方法将GSKIP(糖原合成酶激酶3β相互作用蛋白)确定为AKAP。GSKIP直接与PKA和GSK3β(糖原合成酶激酶3β)相互作用。它被广泛表达，并促进PKA对GSK3β的磷酸化，从而使其失活。GSKIP包含未知功能727的进化保守结构域。我们在这里表明，GSKIP的这个结构域及其脊椎动物同源基因结合了PKA和GSK3β，从而为PKA和GSK3β信号通路的整合提供了一种机制。
A-kinase anchoring proteins (AKAPs) include a family of scaffolding proteins that target protein kinase A (PKA) and other signaling proteins to cellular compartments and thereby confine the activities of the associated proteins to distinct regions within cells. AKAPs bind PKA directly. The interaction is mediated by the dimerization and docking domain of regulatory subunits of PKA and the PKA-binding domain of AKAPs. Analysis of the interactions between the dimerization and docking domain and various PKA-binding domains yielded a generalized motif allowing the identification of AKAPs. Our bioinformatics and peptide array screening approaches based on this signature motif identified GSKIP (glycogen synthase kinase 3 beta interaction protein) as an AKAP. GSKIP directly interacts with PKA and GSK3 beta (glycogen synthase kinase 3 beta). It is widely expressed and facilitates phosphorylation and thus inactivation of GSK3 beta by PKA. GSKIP contains the evolutionarily conserved domain of unknown function 727. We show here that this domain of GSKIP and its vertebrate orthologues binds both PKA and GSK3 beta and thereby provides a mechanism for the integration of PKA and GSK3 beta signaling pathways.