Ca2+-independent protein kinase C isoforms may modulate parietal cell HCl secretion

Chew, Catherine S.; Zhou, Cheng-Jing; Parente, John A.

doi:10.1152/ajpgi.1997.272.2.g246

Cited by 21 publications

(32 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The complete antagonization by Go¨6976 of the TPA-dependent inhibition of H + secretion revealed the suppressive action of PKC-a. Recently, it has been reported that Go¨6976 (100 nM) had no detectable effect on the carbachol-stimulated AP uptake of rabbit gastric glands (Chew et al, 1997). Although comparing physiological data of parietal cells to gastric glands is only preliminary, we also observed that Go¨6976 at 100 nM had no significant effect on carbachol-induced H + secretion.…”

Section: Discussionsupporting

confidence: 42%

“…In rabbit parietal cells Go¨6976 is assumed to be specific to PKC-a, since other calcium-dependent PKC isoenzymes were not detected by specific antibodies (Nandi et al, 1996;Chew et al, 1997). Selective inhibition of PKC-a by Go¨6976 increased carbachol-evoked H + release up to about one-third.…”

Section: Discussionmentioning

confidence: 99%

“…Intracellular inhibition or activation of PKC was mostly analyzed pharmacologically utilizing cellpermeable inhibitors or activators such as 12-O-tetradecanoyl phorbol-13-acetate (TPA) (Anderson & Hanson, 1985;Muallem et al, 1986;Beil et al, 1987;Brown & Chew, 1987;Chiba et al, 1989;Nandi et al, 1996;Kopp & Pfeiffer, 2000, Fa¨hrmann et al, 2002b. Since the specific roles of PKC isoforms in parietal cells are not well understood, the here results presented address the function of PKC-a, the only member of cPKC (conventional PKC) detected in rabbit parietal cells by immunoblotting (Nandi et al, 1996;Chew et al, 1997), in cholinergically stimulated H + release. PKC isoforms are sequentially activated by calcium and diacylglycerol signals (Newton, 1997;Oancea & Meyer, 1998).…”

Section: Introductionmentioning

confidence: 95%

“…The generated inositol trisphosphate mobilizes Ca 2+ from the endoplasmatic reticulum. In parietal cells, free intracellular Ca 2+ stimulates signalling pathways involving protein kinase C (PKC) (Brown & Chew, 1987;Chiba et al, 1989;Nandi et al, 1996;reviewed in Fa¨hrmann, 2000) and Ca 2+ / calmodulin-dependent protein kinase II (CaMKII) (Tsunoda et al, 1992;Fa¨hrmann et al, 2002a,b), respectively, which are both abundant in gastric parietal cells (Mayer et al, 1994;Nandi et al, 1996Nandi et al, , 1999Chew et al, 1997;Fa¨hrmann et al, 1998;2002a;Fa¨hrmann & Pfeiffer, 2000).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Protein kinase C‐α attenuates cholinergically stimulated gastric acid secretion of rabbit parietal cells

Fährmann

Kaufhold

Pfeiffer³

et al. 2003

British J Pharmacology

View full text Add to dashboard Cite

1 The phorbolester 12-O-tetradecanoyl phorbol-13-acetate (TPA), an activator of protein kinase C (PKC), inhibits cholinergic stimulation of gastric acid secretion. We observed that this effect strongly correlated with the inhibition of Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) activity in rabbit parietal cells. 2 The aim of this study was to specify the function of PKC-a in cholinergically stimulated H + secretion. PKC-a represents the only calcium-dependent PKC isoenzyme that has been detected in rabbit parietal cells. 3 Go¨6976, an inhibitor of calcium-dependent PKC, concentration-dependently antagonized the inhibitory effect of TPA, and, therefore, revealed the action of PKC-a on carbachol-induced acid secretion in rabbit parietal cells. 4 TPA exerted no additive inhibition of carbachol-stimulated acid secretion if acid secretion was partially inhibited by the potent CaMKII inhibitor 1-[N,O-bis(5-isoquinolinsulfonyl)-N-methyl-L-tyrosyl]-4-phenyl-piperazine (KN-62). 5 Since both kinase modulators, TPA and KN-62, affected no divergent signal transduction pathways in the parietal cell, an in vitro model has been used to study if PKC directly targets CaMKII. CaMKII purified from parietal cell-containing gastric mucosa of pig, was transphosphorylated by purified cPKC containing PKC-a up to 1.8 mol P i per mol CaMKII in vitro. The autonomy site of CaMKII was not transphosphorylated by PKC. 6 The phosphotransferase activity of the purified CaMKII was in vitro inhibited after transphosphorylation by PKC if calmodulin was absent during transphosphorylation. Attenuation of CaMKII activity by PKC showed strong similarity to the downregulation of CaMKII by basal autophosphorylation. 7 Our results suggest that PKC-a and CaMKII are closely functionally linked in a cholinergically induced signalling pathway in rabbit parietal cells. We assume that in cholinergically stimulated parietal cells PKC-a transinhibits CaMKII activity, resulting in an attenuation of acid secretion.

show abstract

Section: Discussionsupporting

confidence: 42%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Protein kinase C‐α attenuates cholinergically stimulated gastric acid secretion of rabbit parietal cells

Fährmann

Kaufhold

Pfeiffer³

et al. 2003

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Coronin se was initially identified as pp66, a cholinergically regulated, PKC-dependent phosphoprotein in the HCl-secreting gastric parietal cell (11,12). In this study, we present evidence that pp66/coronin se is primarily located in an intracellular canalicular region of parietal cells, which is the site of active HCl secretion.…”

Section: From the Institute Of Molecular Medicine And Genetics Medicmentioning

confidence: 64%

Isolation, Cloning, and Characterization of a New Mammalian Coronin Family Member, Coroninse, Which Is Regulated within the Protein Kinase C Signaling Pathway

Parente

Chen

Zhou

et al. 1999

Journal of Biological Chemistry

View full text Add to dashboard Cite

In order to understand the regulatory role of protein kinase C (PKC) in secretory epithelia, it is necessary to identify and characterize specific downstream targets. We previously identified one such protein in studies of gastric parietal cells. This protein was referred to as pp66 because it migrated with an apparent molecular mass of 66 kDa on SDS-polyacrylamide gels. The phosphorylation of pp66 is increased by the cholinergic agonist, carbachol, and by the PKC activator, phorbol-12-myristate-13-acetate, in a calcium-independent manner. In this study, we have purified pp66 to homogeneity and cloned the complete open reading frame. GenBank TM searches revealed a 45% homology with the Dictyostelium actin-binding protein, coronin, and ϳ67% homology with the previously cloned human and bovine coronin-like homologue, p57. pp66 appears to be most highly expressed in the gastrointestinal mucosa and in kidney and lung. Confocal microscopic studies of an enhanced green fluorescent protein fusion construct of pp66 in cultured parietal cells and in Madin-Darby canine kidney cells indicate that pp66 preferentially localizes in F-actin-rich regions. On the basis of our findings, we propose that pp66 may play an important, PKC-dependent role in regulating membrane/cytoskeletal rearrangements in epithelial cells. We have tentatively named this protein coronin se , because it appears to be highly expressed in secretory epithelia.

show abstract

Coronin proteins as multifunctional regulators of the cytoskeleton and membrane trafficking

2005

View full text Add to dashboard Cite

Coronins constitute an evolutionarily conserved family of WD-repeat actin-binding proteins, which can be clearly classified into two distinct groups based on their structural features. All coronins possess a conserved basic N-terminal motif and three to ten WD repeats clustered in one or two core domains. Dictyostelium and mammalian coronins are important regulators of the actin cytoskeleton, while the fly Dpod1 and the yeast coronin proteins crosslink both actin and microtubules. Apart from that, several coronins have been shown to be involved in vesicular transport. C. elegans POD-1 and Drosophila coro regulate the actin cytoskeleton, but also govern vesicular trafficking as indicated by mutant phenotypes. In both organisms, defects in cytoskeleton and trafficking lead to severe developmental defects ranging from abnormal cell division to aberrant formation of morphogen gradients. Finally, mammalian coronin 7 appears not to execute any cytoskeleton-related functions, but rather participates in regulating Golgi trafficking. Here, we review recent data providing more insight into molecular mechanisms underlying the regulation of F-actin structures, cytoskeletal rearrangements and intracellular membrane transport by coronin proteins and the way that they might link cytoskeleton with trafficking in development and disease.

show abstract

Ca2+-independent protein kinase C isoforms may modulate parietal cell HCl secretion

Cited by 21 publications

References 0 publications

Protein kinase C‐α attenuates cholinergically stimulated gastric acid secretion of rabbit parietal cells

Protein kinase C‐α attenuates cholinergically stimulated gastric acid secretion of rabbit parietal cells

Isolation, Cloning, and Characterization of a New Mammalian Coronin Family Member, Coroninse, Which Is Regulated within the Protein Kinase C Signaling Pathway

Coronin proteins as multifunctional regulators of the cytoskeleton and membrane trafficking

Contact Info

Product

Resources

About