CAMP dependent phosphorylation

Premont, R., Jacobowitz, O. and Iyengar, R. Lowered responsiveness of the catalyst of adenylyl cyclase to stimulation by Gs in heterologous desensitization a role for cAMP dependent phosphorylation. Endocrinology 131 2774-2783,... 

Other mechanisms have also been implicated in odor adaptation, including cAMP-dependent phosphorylation of ciliary proteins via protein kinase A G-protein-receptor kinase activity (GRK3), possibly via phosphorylation of the OR Ca2+/calmodulin kinase II (CaMKII) phosphorylation of ACIII cGMP and carbon monoxide [ 31 ]. These latter three mechanisms have been particularly linked to longer-lasting forms of adaptation, on the order of tens of seconds (for CaMKII) or minutes (CO/cGMP). Together with the short-term adaptation described above, these various molecular mechanisms provide the OSN with a number of ways to fine-tune odor responses over time. 

Autonomic receptors further regulate calcium influx through the sarcolemma (Fig. 15.1). (3-Adrenergic stimulation results in the association of a catalytic subunit of a G protein coupled to the (3-receptor. This stimulates the enzyme adenylyl cyclase to convert ATP to cyclic adenosine monophosphate (cAMP). Increasing cAMP production results in a cAMP-dependent phosphorylation of the L-type calcium channel and a subsequent increase in the probability of the open state of the channel. This translates to an increase in transsarcolemmal calcium influx during phase 2 (the plateau phase) of the cardiac muscle action potential. The effects of transient increases in intracellular levels of cAMP are tightly con-... 

Fitzgerald, E. M., Okuse, K., Wood, J. N., Dolphin, A. C., Moss, S. J. cAMP-dependent phosphorylation of the tetrodotoxin-resistant voltage-dependent sodium channel SNS, J. Physiol. 1999, 516, 433-446. 

TABLE 12-3 Some Enzymes and Other Proteins Regulated by cAMP-Dependent Phosphorylation (by PKA)... 

Pyruvate kinase is allosterically inhibited by ATP, and the liver isozyme is inhibited by cAMP-dependent phosphorylation. 

A functional map of the Na+ channel a subunits. The transmembrane folding model of the a subunit is depicted with experimentally demonstrated sites of cAMP-dependent phosphorylation (P), interaction of site-directed antibodies that define transmembrane orientation covalent attachment... 

Daubner SC, Lauriano C, Haycock JW, Fitzpatrick PF (1992) Site-directed mutagenesis of serine 40 of rat tyrosine hydroxylase. Effects of dopamine and cAMP-dependent phosphorylation on enzyme activity. J Biol Chem 267 12639 16... 

The biochemical mechanisms by which cAMP-dependent phosphorylation leads to enhanced IR-PTH release remain to be determined. It is of interest, however, that isoproterenol activates phosphorylation of proteins of similar molecular weight in the rat parotid gland (22), while glucagon stimulates phosphorylation of a protein of molecular weight 19,000 in calcitonin-secreting cultured cells from a medullary carcinoma of the rat thyroid (22) It is conceivable that in all three tissues, activation of exocytosis results from a cAMP-dependent phosphorylation of a critical cellular substrate. 

The rate-controlling enzymes in the salvage pathways are the phosphocholine and phosphoethanolamine citidyltransferases. Thus, rat liver cell choline, phosphocholine, and CDP-choline concentrations are 0.23, 1.3, and 0.03 mM, respectively. For the ethanolamine derivatives, these are 1.09, 3.83, and 0.24 mM, respectively. The bottlenecks are clearly in the formation of the CDP derivatives. Phosphocholine citidyltransferase of cytosol is phosphorylated and inactive. Phosphorylation prevents its interaction with the ER. It is activated when it is dephosphorylated and translocated to the ER. cAMP-dependent phosphorylation then promotes its removal from the ER and its inactivation. Ethanolamine... 

Glucagon decreases cholesterol synthesis in isolated hepatocytes [131,132] apparently because it reduces the fraction of hydroxymethylglutaryl-CoA reductase in the active form [131,132], This is due to an increase in reductase kinase activity [133], However, there is no evidence that cAMP-dependent protein kinase phos-phorylates either the reductase, reductase kinase or reductase kinase kinase [134], It has been proposed that the phosphorylation state of these enzymes is indirectly controlled through changes in the activity of protein phosphatase I [132,134], This phosphatase can dephosphorylate and activate the reductase [134,135] and its activity can be controlled by a heat stable inhibitor (inhibitor 1), the activity of which is increased by cAMP-dependent phosphorylation [136,137], Since the phosphorylated forms of acetyl-CoA carboxylase, ATP-citrate lyase, pyruvate kinase, phos-phorylase, phosphorylase kinase and glycogen synthase are also substrates for protein phosphatase I [135], this mechanism could also contribute to their phosphorylation by glucagon. 

In addition to mobilizing internal Ca2+, glucagon promotes the net entry of extracellular Ca2+ into hepatocytes [144,145]. The effect is apparently due to increased influx of Ca2+ through a plasma membrane channel(s) [144,145], but there is also inhibition of the plasma membrane Ca2+ ATPase-pump [150-153], The mechanism by which glucagon stimulates Ca2+ entry is unknown, but it almost certainly involves cAMP since the effect can be mimicked by forskolin, dibutyryl cAMP and /3-adrenergic agonists [144,145]. It may involve cAMP-dependent phosphorylation of a Ca2+ channel analogous to the situation in cardiac and skeletal muscle [154-156], but this is strictly speculative. 

The ketogenic action of glucagon is probably related in part to cAMP-dependent phosphorylation and inactivation of acetyl-CoA carboxylase [125,126], This would... 

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