Heterozygous mutations in cyclic AMP phosphodiesterase-4D (PDE4D) and protein kinase A (PKA) provide new insights into the molecular pathology of acrodysostosis

2014 ◽  
Vol 26 (11) ◽  
pp. 2446-2459 ◽  
Author(s):  
Tadashi Kaname ◽  
Chang-Seok Ki ◽  
Norio Niikawa ◽  
George S. Baillie ◽  
Jonathan P. Day ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Protein Kinase A ◽  
Molecular Pathology ◽  
Cyclic Amp Phosphodiesterase ◽  
Phosphodiesterase 4D ◽  
Kinase A

scholarly journals Subcellular localization and hormone sensitivity of adipocyte cyclic AMP phosphodiesterase

1989 ◽  
Vol 262 (3) ◽  
pp. 867-872 ◽  
Author(s):  
N G Anderson ◽  
E Kilgour ◽  
M D Houslay
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Protein Kinase A ◽  
Membrane Fraction ◽  
Endoplasmic Reticulum Membrane ◽  
Phosphodiesterase Activity ◽  
Cyclic Amp Phosphodiesterase ◽  
Specific Polyclonal Antibody ◽  
Kinase A

Treatment of intact adipocytes with either or both insulin and adrenaline stimulated membrane cyclic AMP phosphodiesterase activity only in the endoplasmic reticulum subfraction. The cyclic GMP-inhibited cyclic AMP phosphodiesterase activity was also found in this fraction. Quantitative Western blotting using a specific polyclonal antibody, raised against the homogeneous ‘dense-vesicle’ cyclic AMP phosphodiesterase from rat liver, identified a single 63 kDa species which was localized in the adipocyte endoplasmic reticulum fraction. The ability of adrenaline to stimulate adipocyte membrane cyclic AMP phosphodiesterase was shown to be mediated via beta-adrenoceptors and not alpha 1-adrenoceptors. Membrane cyclic AMP phosphodiesterase was stimulated by glucagon but not by vasopressin, A23187 or 12-O-tetradecanoylphorbol 13-acetate (TPA). Treatment of adipocytes with either chloroquine or dansyl cadaverine failed to affect the ability of insulin to stimulate cyclic AMP phosphodiesterase activity. Treatment of an isolated adipocyte endoplasmic reticulum membrane fraction with purified protein kinase A increased its cyclic AMP phosphodiesterase activity some 2-fold. When this fraction was treated with purified protein kinase A and [32P]ATP, label was incorporated into a 63 kDa protein which was specifically immunoprecipitated with the antiserum against the liver ‘dense-vesicle’ cyclic AMP phosphodiesterase.

scholarly journals Evidence that glucocorticoid- and cyclic AMP-induced apoptotic pathways in lymphocytes share distal events

1992 ◽  
Vol 12 (8) ◽  
pp. 3600-3608
Author(s):  
D R Dowd ◽  
R L Miesfeld
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Protein Kinase A ◽  
Protein Product ◽  
Single Step ◽  
Mitochondrial Activity ◽  
Isolation And Characterization ◽  
Resistant Phenotype ◽  
Apoptotic Pathways ◽  
Kinase A

WEHI7.2 murine lymphocytes undergo apoptotic death when exposed to glucocorticoids or elevated levels of intracellular cyclic AMP (cAMP), and these pathways are initiated by the glucocorticoid receptor (GR) and protein kinase A, respectively. We report the isolation and characterization of a novel WEHI7.2 variant cell line, WR256, which was selected in a single step for growth in the presence of dexamethasone and arose at a frequency of approximately 10(-10). The defect was not GR-related, as WR256 expressed functional GR and underwent GR-dependent events associated with apoptosis, such as hormone-dependent gene transcription and inhibition of cell proliferation. Moreover, the glucocorticoid-resistant phenotype was stable in culture and did not revert after treatment with 5-azacytidine or upon stable expression of GR cDNA. In addition, WR256 did not exhibit the diminished mitochondrial activity commonly associated with apoptosis. Interestingly, WR256 was also found to be resistant to 8-bromo-cAMP and forskolin despite having normal levels of protein kinase A activity and the ability to induce cAMP-dependent transcription. We examined the steady-state transcript levels of bcl-2, a gene whose protein product acts dominantly to inhibit thymocyte apoptosis, to determine whether elevated bcl-2 expression could account for the resistant phenotype. Our data showed that bcl-2 RNA levels were similar in the two cell lines and not altered by either dexamethasone or 8-bromo-cAMP treatment. These results suggest that WR256 exhibits a "deathless" phenotype and has a unique defect in a step of the apoptotic cascade that may be common to the glucocorticoid- and cAMP-mediated cell death pathways.

scholarly journals Terbutaline, forskolin and cAMP reduce secretion of aqueous humour in the isolated bovine eye

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0244253
Author(s):  
Mohammad Shahidullah ◽  
William Stuart Wilson ◽  
Kazi Rafiq ◽  
Mahmudul Hasan Sikder ◽  
Jannatul Ferdous ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Protein Kinase A ◽  
Aqueous Humour ◽  
Calcium Release ◽  
Drug Effects ◽  
Inhibitory Effect ◽  
Plateau Phase ◽  
Intracellular Ca ◽  
Kinase A

In order to elucidate involvement of cyclic AMP and intracellular Ca2+,[Ca2+]i, in the modulation of aqueous humour formation (AHF), we studied the effects of terbutaline, forskolin and 8-Br-cAMP in the isolated bovine eye. We also studied the interaction of cAMP on calcium signaling in cultured ciliary epithelial (CE) cells. Drug effects on AHF were measured by fluorescein dilution. Drug effects on [Ca2+]i were studied by the fura-2 fluorescence ratio technique. Terbutaline (100 nmol-100 M), forskolin (30 nM-100 M) or 8-Br-cAMP (100 nM– 10 μM), administered in the arterial perfusate produced significant reductions in AHF. The AH reducing effect of terbutaline was blocked by a selective inhibitor of protein kinase A (KT-5720). ATP (100 M) caused a rapid, transient (peak) increase in [Ca2+]i followed by a sustained plateau phase lasting more than 5 minutes. Preincubation of the cells (6 min) with terbutaline, forskolin or 8-Br-cAMP significantly reduced the peak calcium response to ATP. The sustained plateau phase of the response, on the other hand, was augmented by each of the agents. KT-5720 partially reversed the inhibitory effect of terbutaline on the peak and totally inhibited its effect on the plateau phase. These data indicate: (a) that AHF in the bovine eye can be manipulated through cyclic AMP, operating via protein kinase A, (b) that protein kinase A can affect [Ca2+]i homeostasis, (c) that calcium release from the intracellular store, not the entry, affects AHF, and (d) that interaction of [Ca2+]i with cAMP plays a role in modulating AH secretion.

Regulation of the astrocyte resting membrane potential by cyclic AMP and protein kinase A

Glia ◽  
2006 ◽  
Vol 54 (4) ◽  
pp. 316-328 ◽  
Author(s):  
Sally Bolton ◽  
Kirsty Greenwood ◽  
Nicola Hamilton ◽  
Arthur M. Butt
Keyword(s):  
Membrane Potential ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Protein Kinase A ◽  
Resting Membrane Potential ◽  
Kinase A
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