cAMP effector mechanisms. Novel twists for an ‘old’ signaling system

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• 作者：Kopperud ; Reidun ; Krakstad ; Camilla ; Selheim ; Frode ; Dø ; skeland ; Stein Ove
• 关键词：Protein kinase A ; cAMP-dependent protein kinase ; Cyclic AMP ; Epac ; Extracellular signal-regulated kinase ; Rap1 ; Rap2 ; Guanine exchange factor ; cAPK I and II ; cAMP-dependent protein kinase I and II ; Epac ; exchange protein directly activated by cAMP ; PKI ; p
• 刊名：FEBS Letters
• 出版年：2003
• 出版时间：July 3, 2003
• 年：2003
• 卷：546
• 期：1
• 页码：121-126
• 全文大小：288 K

文摘

Cyclic AMP (cAMP) has traditionally been thought to act exclusively through cAMP-dependent protein kinase (cAPK, PKA), but a growing number of cAMP effects are not attributable to general activation of cAPK. At present, cAMP is known also to directly regulate ion channels and the ubiquitous Rap guanine exchange factors Epac 1 and 2. Adding to the sophistication of cAMP signaling is the fact that (1) the cAPK holoenzyme is incompletely dissociated even at saturating cAMP, the level of free R subunit of cAPK being able to regulate the maximal activity of cAPK, (2) cAPK activity can be modulated by oxidative glutathionylation, and (3) cAPK is anchored close to relevant substrates, other signaling enzymes, and local compartments of cAMP. Finally, we will demonstrate an example of fine-tuning of cAMP signaling through synergistic induction of neurite extensions by cAPK and Epac.