Document Detail

Role of protein phosphatases in cyclic AMP-mediated stimulation of hepatic Na+/taurocholate cotransport.
MedLine Citation:
PMID:  9792726     Owner:  NLM     Status:  MEDLINE    
Cyclic AMP has been proposed to stimulate Na+/taurocholate (TC) cotransport in hepatocytes by translocating Na+/TC cotransport polypeptide (Ntcp) to the plasma membrane and to induce Ntcp dephosphorylation. Whether protein phosphatases 1 and 2A (PP1/2A) are involved in the regulation of Na+/TC cotransport by cAMP was investigated in the present study. Okadaic acid and tautomycin, inhibitors of PP1/2A, inhibited cAMP-mediated increases in TC uptake and cytosolic [Ca2+], and only tautomycin inhibited basal TC uptake. Removal of cAMP reversed cAMP-mediated increases in TC uptake and plasma membrane Ntcp mass. Okadaic acid alone increased Ntcp phosphorylation without affecting Ntcp mass in plasma membranes and homogenates. In the presence of okadaic acid, cAMP failed to increase plasma membrane Ntcp mass, induce Ntcp dephosphorylation, and decrease endosomal Ntcp mass. Phosphorylated Ntcp was detectable in endosomes isolated from okadaic acid-treated hepatocytes but not in endosomes from control and cAMP-treated hepatocytes. PP1 was found to be enriched in plasma membranes, whereas PP2A was mostly in the cytosol. Cyclic AMP did not activate either PP1 or PP2A, whereas okadaic acid inhibited primarily PP2A. These results suggest that 1) the effect of cAMP on Na+/TC cotransport is not mediated via either PP1 or PP2A; rather, cAMP-mediated signaling pathway is maintained by PP2A and inhibition of PP2A overrides cAMP-mediated effects, and 2) okadaic acid, by inhibiting PP2A, inhibits cAMP-mediated increases in Na+/TC cotransport by decreasing the ability of cAMP to increase cytosolic [Ca2+]. It is proposed that cAMP-mediated dephosphorylation of Ntcp leads to an increased retention of Ntcp in the plasma membrane, and okadaic acid, by inhibiting PP2A, inhibits cAMP-mediated stimulation of Na+/TC cotransport by reversing the ability of cAMP to increase cytosolic [Ca2+] and to induce Ntcp dephosphorylation.
S Mukhopadhyay; C R Webster; M S Anwer
Related Documents :
6979586 - Polymorphism of serum acid phosphatase in the rat.
6631216 - Inactivation of rat liver hmg-coa reductase phosphatases by polycarboxylic acids.
2838446 - Interactions of androgens and prolactin in the seminal vesicles of mature bonnet monkey...
1729356 - Co-localization of an endocytic marker and acid phosphatase in a tubular/reticular comp...
6226826 - Acid mucopolysaccharides in leprosy lesions.
8977126 - Structural and serological studies of the o-specific polysaccharide of the bacterium pr...
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  273     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1998 Nov 
Date Detail:
Created Date:  1998-12-10     Completed Date:  1998-12-10     Revised Date:  2014-04-03    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  30039-45     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Antifungal Agents / pharmacology
Biological Transport
Calcium / metabolism
Carrier Proteins / drug effects*,  metabolism
Cells, Cultured
Cyclic AMP / pharmacology*
Cytosol / drug effects,  metabolism
Enzyme Inhibitors / pharmacology
Liver / drug effects*,  metabolism
Okadaic Acid / pharmacology
Organic Anion Transporters, Sodium-Dependent*
Phosphoprotein Phosphatases / antagonists & inhibitors,  metabolism*
Spiro Compounds*
Grant Support
Reg. No./Substance:
0/Antifungal Agents; 0/Carrier Proteins; 0/Enzyme Inhibitors; 0/Organic Anion Transporters, Sodium-Dependent; 0/Pyrans; 0/Spiro Compounds; 0/Symporters; 109946-35-2/tautomycin; 145420-23-1/sodium-bile acid cotransporter; 1W21G5Q4N2/Okadaic Acid; E0399OZS9N/Cyclic AMP; EC Phosphatases; SY7Q814VUP/Calcium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Phosphorylation of the cAMP response element-binding protein and activation of transcription by alph...
Next Document:  Role of the putative zinc finger domain of Saccharomyces cerevisiae DNA polymerase epsilon in DNA re...