scholarly journals Involvement of a cyclic adenosine monophosphate-dependent signal in the diet-induced canalicular trafficking of adenosine triphosphate-binding cassette transporter g5/g8

Hepatology ◽  
2015 ◽  
Vol 62 (4) ◽  
pp. 1215-1226 ◽  
Author(s):  
Yasuhiro Yamazaki ◽  
Kenta Yasui ◽  
Takahiro Hashizume ◽  
Arisa Suto ◽  
Ayaka Mori ◽  
...  
Keyword(s):  
Adenosine Triphosphate ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Dependent Signal

Can cerium oxide serve as a phosphodiesterase-mimetic nanozyme?

2019 ◽  
Vol 6 (12) ◽  
pp. 3684-3698 ◽  
Author(s):  
Pavel Janoš ◽  
Jakub Ederer ◽  
Marek Došek ◽  
Jiří Štojdl ◽  
Jiří Henych ◽  
...  
Keyword(s):  
Cerium Oxide ◽  
Adenosine Triphosphate ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Phosphodiester Bonds

Nanoceria accelerates dramatically not only the dephosphorylation of energetically rich biomolecules such as adenosine triphosphate (ATP), but also the cleavage of highly resistant phosphodiester bonds in 3′,5′-cyclic adenosine monophosphate (cAMP).

scholarly journals Molecular Mechanism of Light-Induced Acceleration of the Adenosine Triphosphate Conversion to the Cyclic Adenosine Monophosphate Catalyzed by the Photoactivated Adenylyl Cyclase bPAC

2020 ◽  
Author(s):  
Alexander Nemukhin ◽  
Maria Khrenova ◽  
Anna M. Kulakova
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Adenylyl Cyclase ◽  
Adenosine Triphosphate ◽  
Catalytic Domain ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Bluf Domain ◽  
Dynamics Simulations ◽  
Photoactivated Adenylyl Cyclase

<p>We report the first computational characterization of an optogenetic system composed of two photosensing BLUF (<u>b</u>lue <u>l</u>ight sensor <u>u</u>sing <u>f</u>lavin adenine dinucleotide) domains and two catalytic adenylyl cyclase (AC) domains. Conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP) and pyrophosphate (PPi) catalyzed by ACs coupled with excitation in photosensing domains has emerged in the focus of modern optogenetic applications because of the request in photoregulated enzymes to modulate cellular concentrations of signaling messengers. The photoactivated adenylyl cyclase from the soil bacterium <i>Beggiatoa sp.</i> (bPAC) is an important model showing considerable increase of the ATP to cAMP conversion rate in the catalytic domain after the illumination of the BLUF domain. The 1 μs classical molecular dynamics simulations reveal that the activation of the BLUF domain leading to tautomerization of Gln49 in the chromophore binding pocket results in switching of position of the side chain of Arg278 in the active site of AC. Allosteric signal transmission pathways between Gln49 from BLUF and Arg278 from AC were revealed by the dynamical network analysis. The Gibbs energy profiles of the ATP → cAMP + PPi reaction computed using QM(DFT(ωB97X-D3/6-31G**))/MM(CHARMM) molecular dynamics simulations for both Arg278 conformations in AC clarify the reaction mechanism. In the light-activated system, the corresponding arginine conformation stabilizes the pentacoordinated phosphorus of the α-phosphate group in the transition state, thus lowering the activation energy. Simulations of the bPAC system with the Tyr7Phe replacement in BLUF demonstrate occurrence of both arginine conformations in an equal ratio, explaining the experimentally observed intermediate catalytic activity of the bPAC-Y7F variant as compared with the dark and light states of the wild type bPAC. </p>

Downregulation of JAK3 Protein Levels in T Lymphocytes by Prostaglandin E2 and Other Cyclic Adenosine Monophosphate-Elevating Agents: Impact on Interleukin-2 Receptor Signaling Pathway

Blood ◽  
1999 ◽  
Vol 93 (7) ◽  
pp. 2308-2318 ◽  
Author(s):  
Vladimir Kolenko ◽  
Patricia Rayman ◽  
Biswajit Roy ◽  
Martha K. Cathcart ◽  
John O’Shea ◽  
...  
Keyword(s):  
Signal Transduction ◽  
T Cells ◽  
T Lymphocytes ◽  
Prostaglandin E2 ◽  
Signaling Pathway ◽  
Interleukin 2 ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Naïve T Cells ◽  
Dependent Signal

The Janus kinase, JAK3 plays an important role in interleukin-2 (IL-2)–dependent signal transduction and proliferation of T lymphocytes. Our findings show that prostaglandin E2(PGE2) can inhibit upregulation of JAK3 protein in naive T cells and can downregulate its expression in primed cells. Reduction in JAK3 was selective because expression of other tyrosine kinases (JAK1, p56lck, and p59fyn) and signal transducer and activator of transcription (STAT)5, which are linked to IL-2 receptor (IL-2R) signaling pathway, were not affected. Inhibition of JAK3 may be controlled by intracellular cyclic adenosine monophosphate (cAMP) levels, as forskolin, a direct activator of adenylate cyclase and dibutyryl cAMP (dbcAMP), a membrane permeable analogue of cAMP suppressed JAK3 expression. Moreover, 3-isobutyl-1-methylxanthine (IBMX), an inhibitor of cAMP phosphodiesterase, potentiated PGE2-induced suppression of JAK3. In naive T cells, but not primed T cells, PGE2 and other cAMP elevating agents also caused a modest reduction in surface expression of the common gamma chain (γc) that associates with JAK3. The absence of JAK3, but not IL-2R in T cells correlated with impaired IL-2–dependent signal transduction and proliferation. The alteration in IL-2 signaling included decreased tyrosine phosphorylation and DNA binding activity of STAT5 and poor induction of the c-Myc and c-Jun pathways. In contrast, IL-2–dependent induction of Bcl-2 was unaffected. These findings suggest that suppression of JAK3 levels may represent one mechanism by which PGE2 and other cAMP elevating agents can inhibit T-cell proliferation.

Downregulation of JAK3 Protein Levels in T Lymphocytes by Prostaglandin E2 and Other Cyclic Adenosine Monophosphate-Elevating Agents: Impact on Interleukin-2 Receptor Signaling Pathway

Blood ◽  
1999 ◽  
Vol 93 (7) ◽  
pp. 2308-2318 ◽  
Author(s):  
Vladimir Kolenko ◽  
Patricia Rayman ◽  
Biswajit Roy ◽  
Martha K. Cathcart ◽  
John O’Shea ◽  
...  
Keyword(s):  
Signal Transduction ◽  
T Cells ◽  
T Lymphocytes ◽  
Prostaglandin E2 ◽  
Signaling Pathway ◽  
Interleukin 2 ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Naïve T Cells ◽  
Dependent Signal

Abstract The Janus kinase, JAK3 plays an important role in interleukin-2 (IL-2)–dependent signal transduction and proliferation of T lymphocytes. Our findings show that prostaglandin E2(PGE2) can inhibit upregulation of JAK3 protein in naive T cells and can downregulate its expression in primed cells. Reduction in JAK3 was selective because expression of other tyrosine kinases (JAK1, p56lck, and p59fyn) and signal transducer and activator of transcription (STAT)5, which are linked to IL-2 receptor (IL-2R) signaling pathway, were not affected. Inhibition of JAK3 may be controlled by intracellular cyclic adenosine monophosphate (cAMP) levels, as forskolin, a direct activator of adenylate cyclase and dibutyryl cAMP (dbcAMP), a membrane permeable analogue of cAMP suppressed JAK3 expression. Moreover, 3-isobutyl-1-methylxanthine (IBMX), an inhibitor of cAMP phosphodiesterase, potentiated PGE2-induced suppression of JAK3. In naive T cells, but not primed T cells, PGE2 and other cAMP elevating agents also caused a modest reduction in surface expression of the common gamma chain (γc) that associates with JAK3. The absence of JAK3, but not IL-2R in T cells correlated with impaired IL-2–dependent signal transduction and proliferation. The alteration in IL-2 signaling included decreased tyrosine phosphorylation and DNA binding activity of STAT5 and poor induction of the c-Myc and c-Jun pathways. In contrast, IL-2–dependent induction of Bcl-2 was unaffected. These findings suggest that suppression of JAK3 levels may represent one mechanism by which PGE2 and other cAMP elevating agents can inhibit T-cell proliferation.

The structure of a membrane adenylyl cyclase bound to an activated stimulatory G protein

Science ◽  
2019 ◽  
Vol 364 (6438) ◽  
pp. 389-394 ◽  
Author(s):  
Chao Qi ◽  
Simona Sorrentino ◽  
Ohad Medalia ◽  
Volodymyr M. Korkhov
Keyword(s):  
G Protein ◽  
Catalytic Domain ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Bound State ◽  
Adenylyl Cyclases ◽  
Cellular Processes ◽  
Allosteric Sites ◽  
Stimulatory G Protein ◽  
Dependent Signal

Membrane-integral adenylyl cyclases (ACs) are key enzymes in mammalian heterotrimeric GTP-binding protein (G protein)–dependent signal transduction, which is important in many cellular processes. Signals received by the G protein–coupled receptors are conveyed to ACs through G proteins to modulate the levels of cellular cyclic adenosine monophosphate (cAMP). Here, we describe the cryo–electron microscopy structure of the bovine membrane AC9 bound to an activated G protein αs subunit at 3.4-angstrom resolution. The structure reveals the organization of the membrane domain and helical domain that spans between the membrane and catalytic domains of AC9. The carboxyl-terminal extension of the catalytic domain occludes both the catalytic and the allosteric sites of AC9, inducing a conformation distinct from the substrate- and activator-bound state, suggesting a regulatory role in cAMP production.

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