D-AKAP2, a novel protein kinase A anchoring protein with a putative RGS domain

D-AKAP2, a novel protein kinase A anchoring protein with a putative RGS domain
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DOI:
10.1073/pnas.94.21.11184
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发表时间:
1997-10-14
影响因子:
11.1
通讯作者:
Taylor, SS
Taylor, SS
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Huang, LJS;Durick, K;Taylor, SS

文献摘要

被引文献

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由特定 A 激酶锚定蛋白 (AKAP) 指导的亚细胞定位是 cAMP 依赖性蛋白激酶 (PKA) 区室化的机制。使用双杂交筛选,分离出一种新型 AKAP tvas,由于它与 I 型和 II 型调节亚基相互作用,因此将其定义为双特异性 AKAP 或 D-AKAP1。在此,我们报告了从该筛选中分离出的另一种新型 cDNA 的克隆和表征。 D-AKAP 家族的新成员 D-AKAP2 也结合两种类型的调节亚基。在所有胚胎阶段和所有测试的成人组织中都检测到了 D-AKAP2 的 5 kb 对信息。在大脑、骨骼肌、肾脏和睾丸中,鉴定了 10 kb 的 mRNA。在睾丸中,观察到了几个小 mRNA,因此,D-AKAP2 代表了一个新的蛋白质家族。从小鼠睾丸文库克隆 cDNA 鉴定出全长 D-AKAP2。它由 372 个氨基酸组成,其中包括位于 C 末端的 R 结合片段,即残基 333-372。根据共沉淀测定,R 结合结构域与 R-I α 和 R(II)α 的 N 端二聚化结构域相互作用。在 D-AKAP2 的 N 末端区域附近发现了一个推定的 RGS 结构域。该结构域的存在提出了一种有趣的可能性,即 D-AKAP2 可能与 G α 蛋白相互作用,从而提供质膜信号传导机制与下游激酶之间的联系。
Subcellular localization directed by specific A kinase anchoring proteins (AKAPs) is a mechanism for compartmentalization of cAMP-dependent protein kinase (PKA). Using a two-hybrid screen, a novel AKAP tvas isolated, Because it interacts with both the type I and type II regulatory subunits, it was defined as a dual specific AKAP or D-AKAP1. Here we report the cloning and characterization of another novel cDNA isolated from that screen. This new member of the D-AKAP family, D-AKAP2, also binds both types of regulatory subunits, A message of 5 kb pairs was detected for D-AKAP2 in all embryonic stages and in all adult tissues tested, In brain, skeletal muscle, kidney, and testis, a 10-kb mRNA was identified, In testis, several small mRNAs were observed, Therefore, D-AKAP2 represents a novel family of proteins. cDNA cloning from a mouse testis library identified the full length D-AKAP2. It is composed of 372 amino acids which includes the R binding fragment, residues 333-372, at its C-terminus. Based on coprecipitation assays, the R binding domain interacts with the N-terminal dimerization domain of R-I alpha and R(II)alpha. A putative RGS domain was identified near the N-terminal region of D-AKAP2. The presence of this domain raises the intriguing possibility that D-AKAP2 may interact with a G alpha protein thus providing a link between the signaling machinery at the plasma membrane and the downstream kinase.