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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A-kinase-interacting protein localizes protein kinase A in the nucleus.
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A-kinase-interacting protein localizes protein kinase A in the nucleus.

机译：与A激酶相互作用的蛋白将蛋白激酶A定位在细胞核中。

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摘要

The genetic variability and covalent modifications associated with the amino terminus of the protein kinase A (PKA) catalytic (C) subunit suggest that it may contribute to protein-protein interactions and/or localization. By using a yeast two-hybrid screen, we identified a PKA-interacting protein (AKIP1) that binds to the amino terminus (residues 1-39) of the C subunit of PKA. The interaction was localized to the A helix (residues 14-39) of the C subunit and to the carboxyl terminus of AKIP1. AKIP1 thus defines the amino-terminal A helix of PKA as a protein interaction motif. In normal breast (Hs 578 Bst) and HeLa cells, AKIP1 is present in the nucleus as speckles. A nuclear localization signal (Arg-14 and Arg-15) was identified. Upon stimulation with forskolin, HeLa cells expressing AKIP1 accumulated higher levels of the endogenous C subunit in the nucleus. Deletion of the carboxyl terminus of AKIP1 or overexpression of residues 1-39 of the C subunit abolished nuclear localization of the activated endogenous C subunit. Thus, AKIP1 describes a PKA-interacting protein that can contribute to localization by a mechanism that is distinct from A-kinase anchoring proteins that interact with the regulatory subunits.
机译：与蛋白激酶A（PKA）催化（C）亚基氨基末端相关的遗传变异性和共价修饰表明，它可能有助于蛋白-蛋白相互作用和/或定位。通过使用酵母双杂交筛选，我们确定了与PKA C亚基的氨基末端（残基1-39）结合的PKA相互作用蛋白（AKIP1）。相互作用定位于C亚基的A螺旋（残基14-39）和AKIP1的羧基末端。 AKIP1因此将PKA的氨基末端A螺旋定义为蛋白质相互作用基序。在正常乳房（Hs 578 Bst）和HeLa细胞中，AKIP1以斑点的形式存在于细胞核中。确定了核定位信号（Arg-14和Arg-15）。受毛喉素刺激后，表达AKIP1的HeLa细胞在细胞核中积累了更高水平的内源C亚基。 AKIP1羧基末端的删除或C亚基的1-39残基的过表达消除了活化的内源C亚基的核定位。因此，AKIP1描述了一种PKA相互作用蛋白，可以通过不同于与调节亚基相互作用的A激酶锚定蛋白的机制来促进定位。

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