Regulation of Ca2+ release by cAMP-dependent protein kinase -: A mechanism for agonist-specific calcium signaling?
Regulation of Ca2+ release by cAMP-dependent protein kinase -: A mechanism for agonist-specific calcium signaling?
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DOI：
10.1054/ceca.1999.0027
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发表时间：
1999-03-01
期刊：
影响因子：
4
通讯作者：
Bugrim, AE
中科院分区：
文献类型：
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作者：
Bugrim, AE
钙是一种普遍存在的第二信使，参与调节许多细胞功能。实现钙信号传导特异性的机制尚不清楚。我们认为，钙释放从ER可以选择性地发生在不同的空间位置，以响应不同的细胞外刺激。我们讨论了一种可能的机制，这种选择性，并提出了一个模型的基础上，这种机制。该机制基于环腺苷酸依赖性蛋白激酶（PKA）对局部Ca ~（2+）释放的调节，并依赖于两个实验观察：第一，一些G蛋白偶联信号通路激活PLC并同时调节腺苷酸环化酶，导致IP_3产生，并通过cAMP水平的变化改变PKA活性;第二，PKA磷酸化改变IP_3受体（IP_3R）的性质。在我们的模型中，我们考虑了IP（3）R通过IP 3和cAMP依赖性磷酸化的变构调节。在细胞内不同空间位置的IP（3）Rs和PKA密度的差异允许在每个位置选择性地释放钙，以响应IP（3）和cAMP浓度的特定组合。如果这些第二信使水平的不同组合对不同的细胞外刺激具有特异性，则实现激动剂-反应偶联的特异性。
Calcium is an ubiquitous second messenger that is involved in the regulation of a number of cell functions. The mechanism by which the specificity of calcium signaling is achieved is not well understood. We suggest that calcium release from the ER can occur selectively at different spatial locations in response to different extracellular stimuli. We discuss a possible mechanism for such selectivity and present a model based on this mechanism. The suggested mechanism is based on the regulation of local Ca2+ release by cyclic AMP-dependent protein kinase (PKA) and relies upon two experimental observations: first, some G-protein coupled signaling pathways activate PLC and regulate adenylate cyclase at the same time, leading to IP3 production and altering PKA activity via changes in cAMP level; second, phosphorylation by PKA alters the properties of IP3 receptor (IP3R). In our model we consider allosteric regulation of IP(3)Rs by IP3 and cAMP-dependent phosphorylation. The differences in IP(3)Rs and PKA densities at different spatial locations within the cell allow the release of calcium selectively at each location in response to certain combination of IP3 and cAMP concentration. Specificity of agonist-response coupling is achieved if different combinations in the levels of these second messengers are specific for different extracellular stimuli.