cAMP effector mechanisms. Novel twists for an 'old' signaling system.
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.
Kopperud
Reidun
R
Department of Anatomy and Cell Biology, University of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway.
Krakstad
Camilla
C
Selheim
Frode
F
Døskeland
Stein Ove
SO
D000818:Animals; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D011953:Receptors, Cyclic AMP / Q000378:metabolism; D015398:Signal Transduction
D020662:Guanine Nucleotide Exchange Factors; D011953:Receptors, Cyclic AMP; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019204:GTP-Binding Proteins