PMID: 26269590 RLIMS-P 2 Check other iTextMine results Issue Report
Title
1. | The cAMP Signaling Pathway and Direct Protein Kinase A Phosphorylation Regulate Polycystin-2 (TRPP2) Channel Function. |
Abstract
2. | Polycystin-2 (PC2) is a TRP-type, Ca(2+)-permeable non-selective cation channel that plays an important role in Ca(2+) signaling in renal and non-renal cells. |
3. | The effect(s) of the cAMP pathway and kinase mediated phosphorylation of PC2 seem to be relevant to PC2 trafficking and its interaction with polycystin-1. |
4. | However, the role of PC2 phosphorylation in channel function is still poorly defined. |
5. | Here we reconstituted apical membranes of term human syncytiotrophoblast (hST), containing endogenous PC2 (PC2hst), and in vitro translated channel protein (PC2iv). |
6. | Addition of the catalytic subunit of PKA increased by 566% the spontaneous PC2hst channel activity in the presence of ATP. |
7. | Interestingly, 8-Br-cAMP also stimulated spontaneous PC2hst channel activity in the absence of the exogenous kinase. |
8. | Either stimulation was inhibited by addition of alkaline phosphatase, which in turn, was reversed by the phosphatase inhibitor vanadate. |
9. | Neither maneuver modified the single channel conductance but instead increased channel mean open time. |
10. | PKA directly phosphorylated PC2, which increased the mean open time but not the single channel conductance of the channel. |
11. | PKA phosphorylation did not modify either R742X truncated or S829A-mutant PC2iv channel function. |
12. | The data indicate that the cAMP pathway regulates PC2-mediated cation transport in the hST. |
13. | The relevant PKA site for PC2 channel regulation centers on a single residue serine 829, in the carboxyl terminus. |
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