Specificity in the cAMP PKA signaling pathway differential expression regulation and subcellular localization of subunits of PKA

Skålhegg, Bjørn Steen

doi:10.2741/a543

Cited by 156 publications

(198 citation statements)

References 2 publications

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“…Preventing cAMP production by inhibitors of G ␣s (NF449) and AC (ddADP) substantially reduced the Cry1Ab cytotoxicity, whereas the activator (FSK) and potentiator (pCPT-cAMP) of cAMP sensitized the cells and enhanced cytotoxicity. The most common downstream effector of cAMP is PKA (29,32). Pretreatment of S5 cells with inhibitors of PKA (H89 and PKAI 14-22-amide) protected the cells from Cry toxin action.…”

Section: Discussionmentioning

confidence: 99%

“…Second messenger cAMP has been implicated in modulation of signaling related to cell death in a wide variety of cells (29,30). cAMP-dependent signal transduction involves a multiprotein cascade of which many members are Mg 2ϩ -dependent.…”

Section: Correlation Of Cytotoxicity and Elevated Camp Levels Stimulamentioning

confidence: 99%

“…The production of cAMP is controlled by activation of AC, which is stimulated by G ␣s (31). cAMP then binds to cytoplasmic PKA, activating the catalytic subunit(s) of the protein that, in turn, phosphorylates effector proteins (29,32). Mg 2ϩ is required for G protein stimulation through GTP exchange and subunit dissociation and ATP binding as well as for catalytic synthesis of cAMP by AC (31,33,34).…”

Section: Correlation Of Cytotoxicity and Elevated Camp Levels Stimulamentioning

confidence: 99%

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A mechanism of cell death involving an adenylyl cyclase/PKA signaling pathway is induced by the Cry1Ab toxin of Bacillus thuringiensis

Zhang

Candas²,

Griko³

et al. 2006

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

366

324

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Many pathogenic organisms and their toxins target host cell receptors, the consequence of which is altered signaling events that lead to aberrant activity or cell death. A significant body of literature describes various molecular and cellular aspects of toxins associated with bacterial invasion, colonization, and host cell disruption. However, there is little information on the molecular and cellular mechanisms associated with the insecticidal action of Bacillus thuringiensis (Bt) Cry toxins. Recently, we reported that the Cry1Ab toxin produced by Bt kills insect cells by activating a Mg 2؉ -dependent cytotoxic event upon binding of the toxin to its receptor BT-R1. Here we show that binding of Cry toxin to BT-R1 provokes cell death by activating a previously undescribed signaling pathway involving stimulation of G protein (G␣s) and adenylyl cyclase, increased cAMP levels, and activation of protein kinase A. Induction of the adenylyl cyclase͞protein kinase A pathway is manifested by sequential cytological changes that include membrane blebbing, appearance of ghost nuclei, cell swelling, and lysis. The discovery of a toxin-induced cell death pathway specifically linked to BT-R1 in insect cells should provide insights into how insects evolve resistance to Bt and into the development of new, safer insecticides.Cry toxin ͉ protein kinase A ͉ cadherin receptor ͉ cAMP ͉ signal transduction

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Section: Discussionmentioning

confidence: 99%

Section: Correlation Of Cytotoxicity and Elevated Camp Levels Stimulamentioning

confidence: 99%

Section: Correlation Of Cytotoxicity and Elevated Camp Levels Stimulamentioning

confidence: 99%

See 1 more Smart Citation

A mechanism of cell death involving an adenylyl cyclase/PKA signaling pathway is induced by the Cry1Ab toxin of Bacillus thuringiensis

Zhang

Candas²,

Griko³

et al. 2006

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

366

324

View full text Add to dashboard Cite

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“…Apart from transcriptional control, direct physical association between Sox9 and CREB, the prototypical downstream transcription factor of the cAMP-dependent Ser/Thr protein kinase A (PKA), was recently demonstrated by Zhao and colleagues [14]. The PKA holoenzyme has a tetrameric structure that consists of a regulatory subunit dimer and 2 catalytic subunits [15]. The key intracellular signalling target for cAMP, PKA is known to phosphorylate the Sox9 protein (at Ser 211), which induces its translocation into the nucleus and enhances its transcriptional activity [16].…”

Section: Introductionmentioning

confidence: 99%

Mechanical loading stimulates chondrogenesis via the PKA/CREB-Sox9 and PP2A pathways in chicken micromass cultures

Juhász

Matta

Somogyi

et al. 2014

Cellular Signalling

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Biomechanical stimuli play important roles in the formation of articular cartilage during early foetal life, and optimal mechanical load is a crucial regulatory factor of adult chondrocyte metabolism and function. In this study, we undertook to analyse mechanotransduction pathways during in vitro chondrogenesis. Chondroprogenitor cells isolated from limb buds of 4-day-old chicken embryos were cultivated as high density cell cultures for 6 days. Mechanical stimulation was carried out by a self-designed bioreactor that exerted uniaxial intermittent cyclic load transmitted by the culture medium as hydrostatic pressure and fluid shear to differentiating cells. The loading scheme (0.05 Hz, 600 Pa; for 30 min) was applied on culturing days 2 and 3, when final commitment and differentiation of chondroprogenitor cells occurred in this model. The applied mechanical load significantly augmented cartilage matrix production and elevated mRNA expression of several cartilage matrix constituents, including collagen type II and aggrecan core protein, as well as matrixproducing hyaluronan synthases through enhanced expression, phosphorylation and nuclear signals of the main chondrogenic transcription factor Sox9. Along with increased cAMP levels, a significantly enhanced protein kinase A (PKA) activity was also detected and CREB, the archetypal downstream transcription factor of PKA signalling, exhibited elevated phosphorylation levels and stronger nuclear signals in response to mechanical stimuli. All the above effects were diminished by the PKA-inhibitor H89. Inhibition of the PKA-independent cAMP-mediators Epac1 and Epac2 with HJC0197 resulted in enhanced cartilage formation, which was additive to that of the mechanical stimulation, implying that the chondrogenesispromoting effect of mechanical load was independent of Epac. At the same time, PP2A activity was reduced following mechanical load and treatments with the PP2A-inhibitor okadaic acid were able to mimic the effects of the intervention. Our results indicate that proper mechanical stimuli augment in vitro cartilage formation via promoting both Juhász and Matta et al. 3 differentiation and matrix production of chondrogenic cells, and the opposing regulation of the PKA/CREB-Sox9 and the PP2A signalling pathways is crucial in this phenomenon.

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“…The second messenger cAMP produced in response to G protein-coupled receptor-mediated stimuli controls a variety of physiological responses through protein kinase A (PKA) 4 (reviewed in Ref. 1).…”

mentioning

confidence: 99%

Splicing Factor Arginine/Serine-rich 17A (SFRS17A) Is an A-kinase Anchoring Protein That Targets Protein Kinase A to Splicing Factor Compartments

Jarnæss

Stokka

Kvissel

et al. 2009

Journal of Biological Chemistry

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Protein kinase A (PKA) is targeted to distinct subcellular localizations by specific protein kinase A anchoring proteins (AKAPs). AKAPs are divided into subclasses based on their ability to bind type I or type II PKA or both. Dual-specificity AKAPs were recently reported to have an additional PKA binding determinant called the RI specifier region. A bioinformatic search with the consensus RI specifier region identified a novel AKAP, the splicing factor arginine/serine-rich 17A (SFRS17A). Here, we show by a variety of protein interaction assays that SFRS17A binds both type I and type II PKA in vitro and inside cells, demonstrating that SFRS17A is a dual-specific AKAP. Moreover, immunofluorescence experiments show that SFRS17A colocalizes with the catalytic subunit of PKA as well as the splicing factor SC35 in splicing factor compartments. Using the E1A minigene splicing assay, we found that expression of wild type SFRS17A conferred regulation of E1A alternative splicing, whereas the mutant SFRS17A, which is unable to bind PKA, did not. Our data suggest that SFRS17A is an AKAP involved in regulation of pre-mRNA splicing possibly by docking a pool of PKA in splicing factor compartments.

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Specificity in the cAMP PKA signaling pathway differential expression regulation and subcellular localization of subunits of PKA

Cited by 156 publications

References 2 publications

A mechanism of cell death involving an adenylyl cyclase/PKA signaling pathway is induced by the Cry1Ab toxin of Bacillus thuringiensis

A mechanism of cell death involving an adenylyl cyclase/PKA signaling pathway is induced by the Cry1Ab toxin of Bacillus thuringiensis

Mechanical loading stimulates chondrogenesis via the PKA/CREB-Sox9 and PP2A pathways in chicken micromass cultures

Splicing Factor Arginine/Serine-rich 17A (SFRS17A) Is an A-kinase Anchoring Protein That Targets Protein Kinase A to Splicing Factor Compartments

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