Cyclic adenosine monophosphate-dependent

Knighton, D.R., Zheng, I, Ten Eyck, L.F., Ashford, V.A., Xuong, N., Taylor, S.S. and Sowadski, . M. Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase (1991) Science 253, 407-413... 

D.R. Knighton, J.H. Zheng, L. TenEyck, N.H. Xuong, S.S. Taylor, and J.M. Sowadski. 1991. Structure of a peptide inhibitor bound to the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase Science 253 414-420. (PubMed)... 

Cyclic adenosine monophosphate-dependent protein kinase is useful for phosphorylation of a.a. residues in mild conditions. The modification makes the soybean proteins soluble in media rich in calcium and improves their emulsifying properties (Seguro and Motoki, 1990). 

In keeping with their proposed cytoskeletal nature, IFPs initially were thought to serve a purely structural role in muscle cells. It was hypothesized that the function of these proteins was to keep other cytoplasmic proteins in proper relationship to one another, as well as to anchor the cytoplasmic contractile apparatus to the cell membrane. Flowever, subsequent developments in cell biology cast considerable doubt on this premise." The intermediate filaments are now known to serve a nucleic acid-binding function moreover, they are susceptible to processing by calcium-activated proteases and are substrates for cyclic adenosine monophosphate-dependent protein kinases. Thus, it has been proposed that all IFPs serve as modulators between extracellular influences governing calcium flux into the cell (and subsequent protease activation) and nuclear function at a transcriptional... 

Y Horibe, K Hosoya, KJ Kim, T Ogiso, VHL Lee. (1997). Polar solute transport across the pigmented rabbit conjunctiva Size dependence and the influence of 8-bromo cyclic adenosine monophosphate. Pharm Res 14 1246-1251. 

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... 

Fig. 6.4 In vitro effects of mutation on desensitization and internalization of the dopamine receptor. Shown here are effects of mutation on dose-dependent intracellular cyclic adenosine monophosphate (cAMP) accumulation (A and B) and binding curves (C and D) for artificial ligand (SCH 23390) using three constructs controls (wild type, A and C) and the Thr360Ala mutant (360, B and D). In the desensitization experiments, cells were preincubated with 10 oA/ dopamine (o) or vehicle ( ) for 20min, and increasing concentrations of dopamine (10 to 10 (iM) were added to assess cAMP accumulation. Note that loss of efficacy and potency seen in wild-type cells (A) disappeared with the Thr360Ala mutation (B). Conversely, internalization, assessed by decrease in SCH23390 binding (C) after pretreatment with lOpM dopamine (o, compared to vehicle ), was essentially unchanged by the Thr360Ala mutation (D)...

TTie second messenger, for example cyclic adenosine monophosphate (cAMP), then activates cAMP-dependent protein kinase which modulates the function of a broad range of membrane receptors, intracellular enzymes, ion channels and transcription factors. 

Action on the CNS depends directly on the dose of administered drug, and can be manifested as fatigue, anxiety, tremors, and even convulsions in relatively high doses. Theophylline acts on the cardiovascular system by displaying positive ionotropic and chronotropic effects on the heart, which, can likely be linked to the elevated influx of calcium ions by modulated cyclic adenosine monophosphate and its action on specific cardiac phosphodiesterases. In the gastrointestinal system, methylxanthines simultaneously stimulate secretion of both gastric juice and digestive enzymes. 

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-... 

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