scholarly journals The β‐adrenergic stimulation of the renal NaCl cotransporter is mediated via a cAMP‐dependent activation of protein phosphatase 1 inhibitor 1

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
David Penton Ribas ◽  
Sandra Moser ◽  
Agnieszka Wengi ◽  
Jan Czogalla ◽  
Lena Lindtoft Rosenbaek ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Protein Phosphatase 1 ◽  
Adrenergic Stimulation ◽  
Nacl Cotransporter ◽  
Stimulation Of

scholarly journals Protein Phosphatase 1 Inhibitor–1 Mediates the cAMP-Dependent Stimulation of the Renal NaCl Cotransporter

2019 ◽  
Vol 30 (5) ◽  
pp. 737-750 ◽  
Author(s):  
David Penton ◽  
Sandra Moser ◽  
Agnieszka Wengi ◽  
Jan Czogalla ◽  
Lena Lindtoft Rosenbaek ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Mdck Cells ◽  
Ex Vivo ◽  
Phosphorylation Site ◽  
Mouse Kidney ◽  
Protein Phosphatase 1 ◽  
Endocrine Disorders ◽  
Kidney Slices ◽  
Nacl Cotransporter ◽  
Stimulation Of

BackgroundA number of cAMP-elevating hormones stimulate phosphorylation (and hence activity) of the NaCl cotransporter (NCC) in the distal convoluted tubule (DCT). Evidence suggests that protein phosphatase 1 (PP1) and other protein phosphatases modulate NCC phosphorylation, but little is known about PP1’s role and the mechanism regulating its function in the DCT.MethodsWe used ex vivo mouse kidney preparations to test whether a DCT-enriched inhibitor of PP1, protein phosphatase 1 inhibitor–1 (I1), mediates cAMP’s effects on NCC, and conducted yeast two-hybrid and coimmunoprecipitation experiments in NCC-expressing MDCK cells to explore protein interactions.ResultsTreating isolated DCTs with forskolin and IBMX increased NCC phosphorylation via a protein kinase A (PKA)–dependent pathway. Ex vivo incubation of mouse kidney slices with isoproterenol, norepinephrine, and parathyroid hormone similarly increased NCC phosphorylation. The cAMP-induced stimulation of NCC phosphorylation strongly correlated with the phosphorylation of I1 at its PKA consensus phosphorylation site (a threonine residue in position 35). We also found an interaction between NCC and the I1-target PP1. Moreover, PP1 dephosphorylated NCC in vitro, and the PP1 inhibitor calyculin A increased NCC phosphorylation. Studies in kidney slices and isolated perfused kidneys of control and I1-KO mice demonstrated that I1 participates in the cAMP-induced stimulation of NCC.ConclusionsOur data suggest a complete signal transduction pathway by which cAMP increases NCC phosphorylation via a PKA-dependent phosphorylation of I1 and subsequent inhibition of PP1. This pathway might be relevant for the physiologic regulation of renal sodium handling by cAMP-elevating hormones, and may contribute to salt-sensitive hypertension in patients with endocrine disorders or sympathetic hyperactivity.

scholarly journals N-Acetyl-β-D-glucopyranosylamine 6-phosphate is a specific inhibitor of glycogen-bound protein phosphatase 1

1997 ◽  
Vol 328 (2) ◽  
pp. 695-700 ◽  
Author(s):  
Mary BOARD
Keyword(s):  
Phosphatase Activity ◽  
Protein Phosphatase ◽  
Glycogen Phosphorylase ◽  
Glycogen Synthase ◽  
Specific Inhibitor ◽  
Competitive Inhibitor ◽  
Protein Phosphatase 1 ◽  
P Concentration ◽  
Glucose Analogue ◽  
Stimulation Of

Previous work has shown that the C-1-substituted glucose-analogue N-acetyl-β-D-glucopyranosylamine (1-GlcNAc) is a competitive inhibitor of glycogen phosphorylase (GP) and stimulates the inactivation of this enzyme by GP phosphatase. In addition to its effects on GP, 1-GlcNAc also prevents the glucose-led activation of glycogen synthase (GS) in whole hepatocytes. Such an effect on GS was thought to be due to the formation of 1-GlcNAc-6-P by the action of glucokinase within the hepatocyte [Board, Bollen, Stalmans, Kim, Fleet and Johnson (1995) Biochem. J. 311, 845-852]. To investigate this possibility further, a pure preparation of 1-GlcNAc-6-P was synthesized. The effects of the phosphorylated glucose analogue on the activity of protein phosphatase 1 (PP1), the enzyme responsible for dephosphorylation and activation of GS, are reported. During the present study, 1-GlcNAc-6-P inhibited the activity of the glycogen-bound form of PP1, affecting both the GSb phosphatase and GPa phosphatase activities. A level of 50% inhibition of GSb phosphatase activity was achieved with 85 μM 1-GlcNAc-6-P in the absence of Glc-6-P and with 135 μM in the presence of 10 mM Glc-6-P. At either Glc-6-P concentration, 500 μM 1-GlcNAc-6-P completely inhibited activity. The Glc-6-P stimulation of the GPa phosphatase activity of PP1 was negated by 1-GlcNAc-6-P but there was no inhibition of the basal rate in the absence of Glc-6-P. 1-GlcNAc-6-P inhibition was specific for the glycogen-bound form of PP1 and did not inhibit the GSb phosphatase activity of the cytosolic form of the enzyme. The present work explains our previous observations on the inactivating effects on GS of incubating whole hepatocytes with 1-GlcNAc. These observations have their basis in the inhibition of glycogen-bound PP1 by 1-GlcNAc-6-P. A novel inhibitor of PP1, specific for the glycogen-bound form of the enzyme, is presented.

Chronic β-adrenergic stimulation reverses depressed Ca handling in mice overexpressing inhibitor-2 of protein phosphatase 1

2018 ◽  
Vol 125 ◽  
pp. 195-204 ◽  
Author(s):  
Uwe Kirchhefer ◽  
Elke Hammer ◽  
Alexander Heinick ◽  
Thomas Herpertz ◽  
Gunnar Isensee ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Protein Phosphatase 1 ◽  
Adrenergic Stimulation

scholarly journals Protein phosphatase 1 Inhibitor‐1 deficiency causes hypotension and reduces the phosphorylation of renal NaCl cotransporter (892.18)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Nicolas Picard ◽  
Katja Trompf ◽  
Chao‐Ling Yang ◽  
R. Miller ◽  
Monique Carrel ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Protein Phosphatase 1 ◽  
Nacl Cotransporter

scholarly journals A human polymorphism of protein phosphatase‐1 inhibitor‐1 is associated with attenuated contractile response of cardiomyocytes to β‐adrenergic stimulation

2008 ◽  
Vol 22 (6) ◽  
pp. 1790-1796 ◽  
Author(s):  
Guoli Chen ◽  
Xiaoyang Zhou ◽  
Persoulla Nicolaou ◽  
Patricia Rodriguez ◽  
Guojie Song ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Contractile Response ◽  
Protein Phosphatase 1 ◽  
Adrenergic Stimulation ◽  
Human Polymorphism

scholarly journals Stimulation of tumor necrosis factor alpha production in human monocytes by inhibitors of protein phosphatase 1 and 2A.

1992 ◽  
Vol 176 (3) ◽  
pp. 897-901 ◽  
Author(s):  
S J Sung ◽  
J A Walters ◽  
S M Fu
Keyword(s):  
Okadaic Acid ◽  
Mrna Stability ◽  
Protein Phosphatase ◽  
Protein Phosphatase 1 ◽  
Tnf Alpha ◽  
Mrna Accumulation ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Stimulation Of

The protein phosphatase 1 and 2A inhibitor, okadaic acid, has been shown to stimulate many cellular functions by increasing the phosphorylation state of phosphoproteins. In human monocytes, okadaic acid by itself stimulates tumor necrosis factor alpha (TNF-alpha) mRNA accumulation and TNF-alpha synthesis. Calyculin A, a more potent inhibitor of phosphatase 1, has similar effects. TNF-alpha mRNA accumulation in okadaic acid-treated monocytes is due to increased TNF-alpha mRNA stability and transcription rate. The increase in TNF-alpha mRNA stability is more remarkable in okadaic acid-treated monocytes than the mRNA stability of other cytokines, such as interleukin 1 alpha (IL-1 alpha), IL-1 beta, and IL-6. Gel retardation studies show the stimulation of AP-1, AP-2, and NF-kappa B binding activities in okadaic acid-stimulated monocytes. This increase may correlate with the increase in TNF-alpha mRNA transcription rate. In addition to the stimulation of TNF-alpha secretion by monocytes, okadaic acid appears to modulate TNF-alpha precursor processing, as indicated by a marked increase in the cell-associated 26-kD precursor. These results suggest that active basal phosphorylation/dephosphorylation occurs in monocytes, and that protein phosphatase 1 or 2A is important in regulating TNF-alpha gene transcription, translation, and posttranslational modification.

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