Cloning and mitochondrial localization of full-length D-AKAP2, a protein kinase A anchoring protein
Cloning and mitochondrial localization of full-length D-AKAP2, a protein kinase A anchoring protein
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DOI：
10.1073/pnas.051633398
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发表时间：
2001-03-13
影响因子：
11.1
通讯作者：
Taylor, SS
中科院分区：
文献类型：
--
作者：
Wang, L;Sunahara, RK;Taylor, SS
Differential compartmentalization of signaling molecules in cells and tissues is being recognized as an important mechanism for regulating the specificity of signal transduction pathways. A kinase anchoring proteins (AKAPs) direct the subcellular localization of protein kinase A (PKA) by binding to its regulatory (R) subunits. Dual specific AKAPs (D-AKAPs) interact with both RI and RII. A 372-residue fragment of mouse D-AKAP2 with a 40-residue C-terminal PKA binding region and a putative regulator of G protein signaling (RCS) domain was previously identified by means of a yeast two-hybrid screen. Here, we report: the cloning of full-length human D-AKAP2 (662 residues) with an additional putative RCS domain, and the corresponding mouse protein less the first two exons (617 residues). Expression of D-AKAP2 was characterized by using mouse tissue extracts. Full-length D-AKAP2 from various tissues shows different molecular weights, possibly because of alternative splicing or posttranslational modifications. The cloned human gene product has a molecular weight similar to one of the prominent mouse proteins. In vivo association of D-AKAP2 with PKA in mouse brain was demonstrated by using cAMP agarose pull-down assay. Subcellular localization for endogenous mouse, rat, and human D-AKAP2 was determined by immunocytochemistry, immunohistochemistry, and tissue fractionation. D-AKAP2 from all three species is highly enriched in mitochondria. The mitochondrial localization and the presence of RGS domains in D-AKAP2 may have important implications for its function in PKA and G protein signal transduction.
