Membrane-bound cAMP-dependent protein kinase controls cAMP-induced differentiation in PC12 cells
Membrane-bound cAMP-dependent protein kinase controls cAMP-induced differentiation in PC12 cells
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DOI：
10.1074/jbc.274.46.32574
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发表时间：
1999-11-12
影响因子：
4.8
通讯作者：
Avvedimento, EV
中科院分区：
文献类型：
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作者：
Cassano, S;Di Lieto, A;Avvedimento, EV
A126细胞系是PC12的衍生物，在cAMP诱导的转录中有缺陷，并且在cAMP存在下不分化。在这些细胞中，cAMP依赖性蛋白激酶（PKA）的锚蛋白，AKAP 75，和PKA催化亚基的过度表达大大增加了PKA III结合到膜的分数，刺激cAMP诱导的基因的转录，并诱导终末分化。相反，表达AKAP 75蛋白的衍生物AKAP 45的野生型PC12细胞，其结合PKA调节亚基RII，但不能将它们定位到膜，诱导PKA II易位到胞质溶胶。当用cAMP刺激时，这些细胞不能有效地在细胞核中积累PRA催化亚基，不能转录cAMP诱导的基因，并且当暴露于cAMP时不能分化。这些数据表明，膜结合PKA积极控制cAMP诱导的基因的转录和分化的PC12细胞。
The A126 cell line, a derivative of PC12, is defective in cAMP-induced transcription and does not differentiate in the presence of cAMP. In these cells overexpression of a cAMP-dependent protein kinase (PKA) anchor protein, AKAP75, and of the PKA catalytic subunit substantially increased the fraction of PKAIII bound to the membrane, stimulated the transcription of cAMP-induced genes, and induced terminal differentiation. Conversely, wild type PC12 cells expressing a derivative of the AKAP75 protein, AKAP45, which binds the PKA regulatory subunits RII, but fails to locate them to the membranes, induced translocation of PKAII to the cytosol, These cells did not efficiently accumulate PRA catalytic subunit in the nuclei when stimulated with CAMP, did not transcribe cAMP-induced genes, and failed to differentiate when exposed to cAMP. These data indicate that membrane-bound PKA positively controls the transcription of cAMP-induced genes and differentiation in PC12 cells.