CAMP-dependent protein kinase pathway

Xue, J.-F., Liu, Z.-J., Hu, J.-F., Chen, H., Zhang, J.-T., and Chen, N.-H. (2006). Ginsenoside Rbl promotes neurotransmitter release by modulating phosphyrolation of synapsis through a cAMP-dependent protein kinase pathway. Brain Res. 1106, 91-98. 

Pyruvate kinase possesses allosteric sites for numerous effectors. It is activated by AMP and fructose-1,6-bisphosphate and inhibited by ATP, acetyl-CoA, and alanine. (Note that alanine is the a-amino acid counterpart of the a-keto acid, pyruvate.) Furthermore, liver pyruvate kinase is regulated by covalent modification. Flormones such as glucagon activate a cAMP-dependent protein kinase, which transfers a phosphoryl group from ATP to the enzyme. The phos-phorylated form of pyruvate kinase is more strongly inhibited by ATP and alanine and has a higher for PEP, so that, in the presence of physiological levels of PEP, the enzyme is inactive. Then PEP is used as a substrate for glucose synthesis in the pathway (to be described in Chapter 23), instead... 

Dl-iike receptors activate the Gs transduction pathway, stimulating the production of adenylyl cyclase, which increases the formation of cyclic adenosine monophosphate (cAMP) and ultimately increases the activity of cAMP-dependent protein kinase (PKA). PKA activates DARPP-32 (dopamine and cyclic adenosine 3, 5 -monophosphate-regulated phosphoprotein, 32 kDa) via phosphorylation, permitting phospho-DARPP-32 to then inhibit protein phosphatase-1 (PP-1). The downstream effect of decreased PP-1 activity is an increase in the phosphorylation states of assorted downstream effector proteins regulating neurotransmitter... 

Cyclic nucleotides are made in response to receptor activation. The receptor activates a G-protein that, in turn, activates adenylyl cyclase to make the cyclic nucleotide. To complete the signaling, the increase in cAMP concentration activates a specific protein kinase (serine/threo-nine), cAMP-dependent protein kinase (A kinase) (Fig. 9-7). To turn off the signaling pathway, the cyclic nucleotides are destroyed by enzymes called phosphodiesterases. These cleave cAMP to AMP. 

Lorenz, M., Wessler, S., Follmann, E., Michaelis, W., Dusterhoft, T., Baumann, G., Stangl, K, and Stangl, V., A constituent of green tea, epigallocatechin-3-gallate, activates rndothelial nitric oxide synthase by a phosphatidylinositol-3-OH-kinase-, cAMP-dependent protein kinase-, and Akt-dependent pathway and leads to endothelial-dependent vasorelaxation, J. Biol Chem., 279, 6190, 2004. 

Figure 1.11 Pathways involved in phospholipase C (PLC) cellular signalling. PKA, protein kinase A or cAMP-dependent protein kinases PKC, protein kinase C PI, phosphatidylinositol PIP2, phosphatidylinositol bis-phosphate IP3, inositol triphosphate IP, inositol phosphate DAG, diacylglycerol.

Apart from exocytosis, presynaptic H3 autoreceptors also inhibit the synthesis of histamine at the level of nerve endings, at least in part through pathways distinct from those leading to the inhibition of release. One pathway is inhibition of adenylyl cyclase (Gomez-Ramirez et al. 2002 Moreno-Delgado et al. 2006) activation of cAMP-dependent protein kinase A by cAMP stimulates histamine synthesis through phosphorylation of histidine decarboxylase, and this stimulation is diminished when adenylyl cyclase activity decreases following activation of H3 autoreceptors and Gi/o proteins. 

---