Molecular mechanisms of feedback inhibition of protein kinase A on intracellular cAMP accumulation

Vandamme, Jurgen; Castermans, Dries; Thevelein, Johan M.

doi:10.1016/j.cellsig.2012.04.001

Cited by 55 publications

(55 citation statements)

References 158 publications

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“…Interestingly, the dissociation of the bait and prey exhibited an adaptive response, presumably owing to receptor desensitization and hydrolysis of cAMP by phosphodiesterases. [9] The b-adrenergic receptor antagonist, propranolol, further increased the bait/ prey interaction. Subsequent receptor stimulation using isoproterenol could not reactivate the system.…”

Section: Methodsmentioning

confidence: 99%

“…This high level of cell-to-cell variance can be explained by adaptive mechanisms in the underlying signal networks. [9] Because of this variance, relations in response properties between the regulatory subunits, such as their interaction efficiency in resting cells (Figure 2 d) or their temporal cross-correlation profiles (Figure 2 e), are blurred in measurements averaged from many cells. This is overcome by measuring the dynamic response profiles of the interaction between the catalytic and the two distinct regulatory subunits simultaneously in individual cells.…”

Section: Methodsmentioning

confidence: 99%

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A Protein‐Interaction Array Inside a Living Cell

et al. 2013

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

A Protein‐Interaction Array Inside a Living Cell

et al. 2013

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“…This kinase controls cellular homeostasis by coordinating energy metabolism, cellular growth, autophagy, differentiation, aging, stress response, and responses to many external stimuli in fungi and mammals (8)(9)(10)(11)(12). Improper regulation of the enzyme is associated with severe phenotypes and diseases in humans (13) and loss of virulence in pathogenic fungi (14).…”

mentioning

confidence: 99%

“…However, the inbound and feedback signals this kinase integrates are not entirely known or well understood beyond the canonical Ras/cAMP and G protein-coupled receptor GPCR pathways (15), particularly in fungi. Direct mechanisms of PKA regulation include cAMP binding to the R subunits (8), phosphorylation (16), and subcellular localization of its subunits (17). In mammalian cells, there is extensive evidence for compartmentalization of cAMP signaling in which A kinase-anchoring proteins (AKAPs) play a major role by coupling PKA to a variety of other enzymes (9).…”

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confidence: 99%

Systematic identification of signal integration by protein kinase A

Filteau

Diss

Torres-Quiroz

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Cellular processes and homeostasis control in eukaryotic cells is achieved by the action of regulatory proteins such as protein kinase A (PKA). Although the outbound signals from PKA directed to processes such as metabolism, growth, and aging have been well charted, what regulates this conserved regulator remains to be systematically identified to understand how it coordinates biological processes. Using a yeast PKA reporter assay, we identified genes that influence PKA activity by measuring proteinprotein interactions between the regulatory and the two catalytic subunits of the PKA complex in 3,726 yeast genetic-deletion backgrounds grown on two carbon sources. Overall, nearly 500 genes were found to be connected directly or indirectly to PKA regulation, including 80 core regulators, denoting a wide diversity of signals regulating PKA, within and beyond the described upstream linear pathways. PKA regulators span multiple processes, including the antagonistic autophagy and methionine biosynthesis pathways. Our results converge toward mechanisms of PKA posttranslational regulation by lysine acetylation, which is conserved between yeast and humans and that, we show, regulates protein complex formation in mammals and carbohydrate storage and aging in yeast. Taken together, these results show that the extent of PKA input matches with its output, because this kinase receives information from upstream and downstream processes, and highlight how biological processes are interconnected and coordinated by PKA.Ras/cAMP/PKA pathway | acetylation | methionine | autophagy | TOR

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“…cAMP is produced by adenylate cyclase (AC), a 12-transmembrane-spanning enzyme that catalyzes the conversion of ATP to 3Ј,5Ј-cAMP and pyrophosphate (11). Cellular phosphodiesterases then degrade newly synthesized cAMP by hydrolyzing the phosphodiester bonds to produce 5ЈAMP (12).…”

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confidence: 99%

Forskolin-inducible cAMP Pathway Negatively Regulates T-cell Proliferation by Uncoupling the Interleukin-2 Receptor Complex

Rodriguez

Ross

Nagy

et al. 2013

Journal of Biological Chemistry

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Background: Within activated T-cells, the binding of IL-2 to its receptor initiates the Jak3/Stat5 cascade culminating in proliferation. Results: Elevated levels of cAMPi within activated T-cells suppresses proliferation by targeting multiple levels of the IL-2R cascade. Conclusion: Cross-talk occurs between cAMP/PKA and the IL-2R/Jak3/Stat5 cascade in human T-cells. Significance: Therapeutic potential exists in manipulating the described cross-talk for the treatment of various immune diseases.

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Molecular mechanisms of feedback inhibition of protein kinase A on intracellular cAMP accumulation

Cited by 55 publications

References 158 publications

A Protein‐Interaction Array Inside a Living Cell

A Protein‐Interaction Array Inside a Living Cell

Systematic identification of signal integration by protein kinase A

Forskolin-inducible cAMP Pathway Negatively Regulates T-cell Proliferation by Uncoupling the Interleukin-2 Receptor Complex

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