scholarly journals Imiquimod directly inhibits Hedgehog signalling by stimulating adenosine receptor/protein kinase A-mediated GLI phosphorylation

Oncogene ◽  
2013 ◽  
Vol 32 (50) ◽  
pp. 5574-5581 ◽  
Author(s):  
F Wolff ◽  
A Loipetzberger ◽  
W Gruber ◽  
H Esterbauer ◽  
F Aberger ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Adenosine Receptor ◽  
Receptor Protein ◽  
Hedgehog Signalling ◽  
Kinase A

scholarly journals AKAP79 enables calcineurin to directly suppress protein kinase A activity

2021 ◽  
Author(s):  
Timothy W. Church ◽  
Parul Tewatia ◽  
Saad Hannan ◽  
João Antunes ◽  
Olivia Eriksson ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Hippocampal Neurons ◽  
Second Messengers ◽  
Capture Rate ◽  
Receptor Protein ◽  
Regulatory Subunits ◽  
Cellular Processes ◽  
Order Of Magnitude ◽  
Kinase A

Interplay between the second messengers cAMP and Ca2+ is a hallmark of dynamic cellular processes. A common motif is the opposition of the Ca2+-sensitive phosphatase calcineurin and the major cAMP receptor, protein kinase A (PKA). Calcineurin dephosphorylates sites primed by PKA to bring about changes including synaptic long-term depression (LTD). AKAP79 supports signaling of this type by anchoring PKA and calcineurin in tandem. In this study, we discovered that AKAP79 increases the rate of calcineurin dephosphorylation of type II PKA regulatory subunits by an order of magnitude. Fluorescent PKA activity reporter assays, supported by kinetic modeling, show how AKAP79-enhanced calcineurin activity enables suppression of PKA without altering cAMP levels by increasing PKA catalytic subunit capture rate. Experiments with hippocampal neurons indicate that this mechanism contributes towards LTD. This non-canonical mode of PKA regulation may underlie many other cellular processes.

scholarly journals AKAP79 enables calcineurin to directly suppress protein kinase A activity

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Timothy W Church ◽  
Parul Tewatia ◽  
Saad Hannan ◽  
João Antunes ◽  
Olivia Eriksson ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Hippocampal Neurons ◽  
Second Messengers ◽  
Capture Rate ◽  
Receptor Protein ◽  
Regulatory Subunits ◽  
Cellular Processes ◽  
Order Of Magnitude ◽  
Kinase A

Interplay between the second messengers cAMP and Ca2+ is a hallmark of dynamic cellular processes. A common motif is the opposition of the Ca2+-sensitive phosphatase calcineurin and the major cAMP receptor, protein kinase A (PKA). Calcineurin dephosphorylates sites primed by PKA to bring about changes including synaptic long-term depression (LTD). AKAP79 supports signaling of this type by anchoring PKA and calcineurin in tandem. In this study, we discovered that AKAP79 increases the rate of calcineurin dephosphorylation of type II PKA regulatory subunits by an order of magnitude. Fluorescent PKA activity reporter assays, supported by kinetic modeling, show how AKAP79-enhanced calcineurin activity enables suppression of PKA without altering cAMP levels by increasing PKA catalytic subunit capture rate. Experiments with hippocampal neurons indicate that this mechanism contributes towards LTD. This non-canonical mode of PKA regulation may underlie many other cellular processes.

Hedgehog signalling activity of Smoothened requires phosphorylation by protein kinase A and casein kinase I

Nature ◽  
2004 ◽  
Vol 432 (7020) ◽  
pp. 1045-1050 ◽  
Author(s):  
Jianhang Jia ◽  
Chao Tong ◽  
Bing Wang ◽  
Liping Luo ◽  
Jin Jiang
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Casein Kinase ◽  
Casein Kinase I ◽  
Hedgehog Signalling ◽  
Kinase A

scholarly journals A Multistep Kinase-Based Sertoli Cell Autocrine-Amplifying Loop Regulates Prostaglandins, Their Receptors, and Cytokines

Endocrinology ◽  
2006 ◽  
Vol 147 (4) ◽  
pp. 1706-1716 ◽  
Author(s):  
Tomomoto Ishikawa ◽  
Patricia L. Morris
Keyword(s):  
Protein Synthesis ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Receptor Activation ◽  
Cytokine Expression ◽  
Receptor Expression ◽  
Receptor Protein ◽  
Prostanoid Receptor ◽  
Cox 2 ◽  
Kinase A

In Sertoli epithelial cells, the IL-1β induces prostaglandins (PG) PGE2, PGF2α and PGI2 (7-, 11-, and 2-fold, respectively), but not PGD2, production. Cyclohexamide pretreatment inhibiting protein synthesis prevents IL-1β increases in PG levels, indicating that induction requires de novo protein synthesis. IL-1β-regulated PGE2 and PGF2α production and cytokine expression require activation of cyclooxygenase-2 (COX-2) and c-Jun NH2-terminal kinase, as shown using specific enzyme inhibition. PGE2 and PGF2α stimulate expression of IL-1α, -1β, and -6, findings consistent with PG involvement in IL signaling within the seminiferous tubule. PGE2 and PGF2α reverse COX-2-mediated inhibition of IL-1β induction of cytokine expression and PG production. Sertoli PG receptor expression was determined; four known E-prostanoid receptor (EP) subtypes (1–4) and the F-prostanoid and prostacyclin prostanoid receptors were demonstrated using RNA and protein analyses. Pharmacological characterization of Sertoli PG receptors associated with cytokine regulation was ascertained by quantitative real-time RT-PCR analyses. IL-1β regulates both EP2 mRNA and protein levels, data consistent with a regulatory feedback loop. Butaprost (EP2 agonist) and 11-deoxy PGE1 (EP2 and EP4 agonist) treatments show that EP2 receptor activation stimulates Sertoli cytokine expression. Consistent with EP2-cAMP signaling, protein kinase A inhibition blocks both IL-1β- and PGE2-induced cytokines. Together, the data indicate an autocrine-amplifying loop involving IL-1β-regulated Sertoli function mediated by COX-2-induced PGE2 and PGF2α production. PGE2 activates EP2 and/or EP4 receptor(s) and the protein kinase A-cAMP pathway; PGF2α activates F-prostanoid receptor-protein kinase C signaling. Further identification of the molecular mechanisms subserving these mediators may offer new insights into physiological events as well as proinflammatory-mediated pathogenesis in the testis.

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