Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sarcoplasmic reticulum (SR) membrane vesicles derived from human atrium were characterized by specific ryanodine binding assay and fused into planar lipid bilayers. The tritiated form of the alkaloid bound to its receptor with a K(D) of 2.2 nM and a Bmax of 268 fmol/mg protein respectively. Special emphasis was placed on an anion-selective channel present in the SR membrane, which exhibited a mean conductance value of 67 pS when recorded in asymmetrical 50 mM trans/250 mM cis CsCl buffer system and a sensitivity to SITS (1 to 100 microM). Single and multiple channel activities displayed low voltage sensitivity and variability in its gating behavior which might result in spontaneous channel inactivation. However, the majority of the recordings (60%) resulted in a steady-state high open probability. The inactivated channel could be transiently reactivated with depolarizing voltage steps. This behavior is very similar, if not identical, to that observed for the SR Cl- channel in ventricular cells. The inactivation process is probably not directly related to a phosphorylation/dephosphorylation mechanism since PKA and PKG in presence of an adequate phosphorylation cocktail failed to reactivate the SR Cl- channel. In contrast, the use of a monoclonal anti-phospholamban antibody allowed the inhibition of the activity of the anionic channels. These results suggest that the regulation of the human atrial SR Cl- channel is dependent upon an interaction with phospholamban, which was clearly identified in our atrial preparations by Western blot analysis using monoclonal antibody.
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PMID:Biochemical regulation of sarcoplasmic reticulum Cl- channel from human atrial myocytes: involvement of phospholamban. 873 4

In the cortical collecting duct of the rat two Ca(2+)-dependent K+ channels have been described so far. In the luminal membrane a maxi K+ channel with a single channel conductance of 139 +/- 3 pS in excised membrane patches (n = 91) at 0 mV clamp voltage and asymmetrical KCl-concentrations in pipette and bath was found, while in the basolateral membrane an intermediate conductance K+ channel (85 +/- 1 pS, n = 53) and a small K+ channel (28 +/- 2 pS, n = 15) was described. All these K+ channels had similar pharmacological properties since all could be blocked by the K+ channel inhibitors Ba2+, TEA+, and charybdotoxin. Verapamil, known as a L-type Ca2+ channel blocker, was also capable of inhibiting these K+ channels. While the maxi K+ channel from the luminal membrane was upregulated by intracellular Ca2+ (EC50: 5 microM), the small and the intermediate K+ channel from the basolateral membrane were downregulated (IC50: 10 microM). When the cytosolic Ca(2+)-activity was in the physiological range below 1 microM the activity of the maxi K+ channel was low and regulated via intracellular pH and ATP. Furthermore, when CCD cells were strongly depolarized and under hypoosmotic stress, Ca2+ rose and activated this K+ channel, indicating that this channel is involved in volume regulation. Like the maxi K+ channel the intermediate conductance K+ channel from the basolateral membrane was also sensitive to intracellular changes of pH where acidic pH inhibited while alkaline pH activated this channel. But unlike the K+ channels from the luminal membrane the K+ channel from the basolateral membrane is not regulated by ATP up to 5 mM. The activity of the K+ channels from the basolateral membrane decreased steadily after excision of the membrane. This decrease could be prevented by applying cGMP and MgATP to the bath and thus, activating a membrane-bound cGMP-dependent protein kinase (PKG). The activation of the PKG could be reversed by its specific inhibitor KT5823 (1 microM). Due to the opposite regulation via intracellular Ca2+ and the involvement of different protein kinases a specific and independent regulation of K+ secretion and Na+ reabsorption is possible in the CCD of the rat.
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PMID:Ca(2+)-dependent K+ channels in the cortical collecting duct of rat. 926 90

The AGCVIIIa kinases of Arabidopsis are members of the eukaryotic PKA, PKG, and PKC group of regulatory kinases. One AGCVIIIa kinase, PINOID (PID), plays a fundamental role in the asymmetrical localization of membrane proteins during polar auxin transport. The remaining 16 AGCVIIIa genes have not been associated with single mutant phenotypes, suggesting that the corresponding kinases function redundantly. Consistent with this idea, we find that the genes encoding the Arabidopsis AGCVIIIa kinases have spatially distinct, but overlapping, expression domains. Here we show that the majority of Arabidopsis AGCVIIIa kinases are substrates for the 3-phosphoinositide-dependent kinase 1 (PDK1) and that trans-phosphorylation by PDK1 correlates with activation of substrate AGCVIIIa kinases. Mutational analysis of two conserved regulatory domains was used to demonstrate that sequences located outside of the C-terminal PDK1 interaction (PIF) domain and the activation loop are required for functional interactions between PDK1 and its substrates. A subset of GFP-tagged AGCVIIIa kinases expressed in Saccharomyces cerevisiae and tobacco BY-2 cells were preferentially localized to the cytoplasm (AGC1-7), nucleus (WAG1 and KIPK), and the cell periphery (PID). We present evidence that PID insertion domain sequences are sufficient to direct the observed peripheral localization. We find that PID specifically but non-selectively binds to phosphoinositides and phosphatidic acid, suggesting that PID might directly interact with the plasma membrane through protein-lipid interactions. The initial characterization of the AGCVIIIa kinases presented here provides a framework for elucidating the physiological roles of these kinases in planta.
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PMID:Structural and functional insights into the regulation of Arabidopsis AGC VIIIa kinases. 1697 27