Role of protein kinase A and class II phosphatidylinositol 3-kinase C2β in the downregulation of KCa3.1 channel synthesis and membrane surface expression by lyso-globotriaosylceramide

2016 ◽  
Vol 470 (4) ◽  
pp. 907-912 ◽  
Author(s):  
Ju Yeon Choi ◽  
Seonghee Park
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Membrane Surface ◽  
Surface Expression ◽  
Class Ii ◽  
Phosphatidylinositol 3 Kinase ◽  
Kinase A ◽  
Phosphatidylinositol 3

scholarly journals Protein kinase A and protein kinase Cα/PPP1CC2 play opposing roles in the regulation of phosphatidylinositol 3-kinase activation in bovine sperm

Reproduction ◽  
2010 ◽  
Vol 140 (1) ◽  
pp. 43-56 ◽  
Author(s):  
T Rotman ◽  
N Etkovitz ◽  
A Spiegel ◽  
S Rubinstein ◽  
H Breitbart
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Phosphatidylinositol 3 Kinase ◽  
Highly Active ◽  
Protein Kinase Cα ◽  
Pi3k Activation ◽  
Kinase A ◽  
Phosphatidylinositol 3

In order to acquire fertilization competence, spermatozoa have to undergo biochemical changes in the female reproductive tract, known as capacitation. Signaling pathways that take place during the capacitation process are much investigated issue. However, the role and regulation of phosphatidylinositol 3-kinase (PI3K) in this process are still not clear. Previously, we reported that short-time activation of protein kinase A (PRKA, PKA) leads to PI3K activation and protein kinase Cα (PRKCA, PKCα) inhibition. In the present study, we found that during the capacitation PI3K phosphorylation/activation increases. PI3K activation was PRKA dependent, and down-regulated by PRKCA. PRKCA is found to be highly active at the beginning of the capacitation, conditions in which PI3K is not active. Moreover, inhibition of PRKCA causes significant activation of PI3K. Similar activation of PI3K is seen when the phosphatase PPP1 is blocked suggesting that PPP1 regulates PI3K activity. We found that during the capacitation PRKCA and PPP1CC2 (PP1γ2) form a complex, and the two enzymes were degraded during the capacitation, suggesting that this degradation enables the activation of PI3K. This degradation is mediated by PRKA, indicating that in addition to the direct activation of PI3K by PRKA, this kinase can enhance PI3K phosphorylation indirectly by enhancing the degradation and inactivation of PRKCA and PPP1CC2.

scholarly journals Prostaglandin E2 induces interleukin-6 expression in human chondrocytes via cAMP/protein kinase A- and phosphatidylinositol 3-kinase-dependent NF-κB activation

2010 ◽  
Vol 298 (6) ◽  
pp. C1445-C1456 ◽  
Author(s):  
Pu Wang ◽  
Fei Zhu ◽  
Konstantinos Konstantopoulos
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Synovial Fibroblasts ◽  
Human Chondrocytes ◽  
Phosphatidylinositol 3 Kinase ◽  
Downstream Effectors ◽  
Mrna And Protein Expression ◽  
Simultaneous Inhibition ◽  
Kinase A ◽  
Phosphatidylinositol 3

Elevated levels of prostaglandin (PG)E2 and interleukin (IL)-6 have been reported in the cartilage and synovial fluid from patients with arthritic disorders. PGE2 regulates IL-6 production in numerous different cells including macrophages and synovial fibroblasts. Although PGE2 stimulates IL-6 expression in human chondrocytes, the underlying signaling pathway of this process has yet to be delineated. Here, we investigate the mechanism of IL-6 induction in human T/C-28a2 chondrocytes treated with exogenously added PGE2. PGE2 induces IL-6 mRNA and protein expression via a cAMP-dependent pathway, reaching maximal levels after 60 min of stimulation before declining to baseline levels at 6 h. Forskolin, an adenylyl cyclase activator, also stimulates IL-6 expression in human chondrocytes in a dose- and time-dependent fashion. Inhibition of downstream effectors of cAMP activity such as protein kinase A (PKA) or phosphatidylinositol 3 kinase (PI3K) blocks PGE2- and forskolin-induced IL-6 upregulation. Simultaneous inhibition of PKA and PI3K reduces IL-6 expression in stimulated chondrocytes well below the basal levels of untreated cells. Gel shift, supershift, and chromatin immunoprecipitation assays reveal the activation and binding of the nuclear factor (NF)-κB p65 subunit to the IL-6 promoter, which is markedly suppressed by selective PI3K or PKA pharmacological inhibitors. p65 knockdown completely abrogates IL-6 mRNA synthesis in PGE2- and forskolin-primed chondrocytes. Cumulatively, our data show that PGE2 and forskolin induce IL-6 expression in human chondrocytes via cAMP/PKA and PI3K-dependent pathways, which in turn regulate the activation and binding of p65 to the IL-6 promoter.

scholarly journals Activation of STAT3 by GαsDistinctively Requires Protein Kinase A, JNK, and Phosphatidylinositol 3-Kinase

2006 ◽  
Vol 281 (47) ◽  
pp. 35812-35825 ◽  
Author(s):  
Andrew M. F. Liu ◽  
Rico K. H. Lo ◽  
Cecilia S. S. Wong ◽  
Christina Morris ◽  
Helen Wise ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Phosphatidylinositol 3 Kinase ◽  
Kinase A ◽  
Phosphatidylinositol 3
Sign in / Sign up

Export Citation Format

Share Document