The calmodulin-dependent phosphodiesterase gene PDE1C encodes several functionally different splice variants in a tissue-specific manner
The calmodulin-dependent phosphodiesterase gene PDE1C encodes several functionally different splice variants in a tissue-specific manner
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DOI：
10.1074/jbc.271.41.25699
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发表时间：
1996-10-11
影响因子：
4.8
通讯作者：
Beavo, JA
中科院分区：
文献类型：
--
作者：
Yan, C;Zhao, AZ;Beavo, JA
我们在这里报告的三个新的小鼠PDE 1C剪接变异体的cDNA的鉴定和表征的动力学，调节钙离子，抑制剂的敏感性，和组织/细胞的表达模式。序列分析表明，这三个cDNA（PDE 1C 1，PDE 1C 4和PDE 1C 5），连同我们以前报道的PDE 1C 2和PDE 1C 3，是PDE 1C基因的选择性剪接产物。从RNA酶保护分析和原位杂交的结果表明，不同的PDE 1C剪接变体的表达差异调节的组织/细胞特异性的方式。特别地，在嗅上皮、睾丸和小鼠脑的几个区域如小脑颗粒细胞中发现了高水平的PDE 1C mRNA。所有这些剪接变体具有相似的动力学性质，显示出高亲和力和对于cAMP和cGMP的大致相同的相对V-max值。此外，它们对钙调素依赖性磷酸二酯酶抑制剂KS 505 a和SCH 51866的敏感性也不同。底物竞争实验表明，这些PDE 1C同工酶的cAMP和cGMP只有一个催化位点的存在。总之，这些研究结果表明，PDE 1C基因经历组织特异性选择性剪接，产生结构和功能多样的基因产物。
We report here the identification of cDNAs for three new mouse PDE1C splice variants and the characterization of their kinetics, regulation by Ca2+, sensitivities to inhibitors, and tissue/cellular expression patterns. Sequence analysis indicated that these three cDNAs (PDE1C1, PDE1C4, and PDE1C5), together with our previously reported PDE1C2 and PDE1C3, are alternative splice products of the PDE1C gene. The results from RNase protection analysis and in situ hybridization indicated that the expression of the different PDE1C splice variants is differentially regulated in a tissue/cell-specific manner. Particularly, high levels of PDE1C mRNAs were found in the olfactory epithelium, testis, and several regions of mouse brain such as cerebellar granule cells, All of these splice variants have similar kinetic properties, showing high affinities and approximately the same relative V-max values for both cAMP and cGMP. However, they responded to Ca2+ stimulation differently, In addition, they show different sensitivities to the calmodulin-dependent phosphodiesterase inhibitors, KS505a and SCH51866. Substrate competition experiments suggested the presence of only one catalytic site on these PDE1C isozymes for both cAMP and cGMP. In summary, these findings suggest that the PDE1C gene undergoes tissue-specific alternative splicing that generates structurally and functionally diverse gene products.