Differential Expression of Protein Kinase C Genes in Cultured Mast Cells Derived from Normal and Mast-Cell-Deficient Mice and Mast Cell Lines

1994 ◽  
Vol 105 (3) ◽  
pp. 258-263 ◽  
Author(s):  
Hyung-Min Kim ◽  
Seiichi Hirota ◽  
Hun-Taeg Chung ◽  
Shigeo Ohno ◽  
Shin-Ichi Osada ◽  
...  
Keyword(s):  
Mast Cell ◽  
Protein Kinase C ◽  
Mast Cells ◽  
Protein Kinase ◽  
Differential Expression ◽  
Cell Lines ◽  
Kinase C ◽  
Deficient Mice

scholarly journals Protein Kinase C-δ Is a Negative Regulator of Antigen-Induced Mast Cell Degranulation

2002 ◽  
Vol 22 (12) ◽  
pp. 3970-3980 ◽  
Author(s):  
Michael Leitges ◽  
Kerstin Gimborn ◽  
Winfried Elis ◽  
Janet Kalesnikoff ◽  
Michael R. Hughes ◽  
...  
Keyword(s):  
Mast Cell ◽  
Protein Kinase C ◽  
Mast Cells ◽  
Protein Kinase ◽  
Sh2 Domain ◽  
Mast Cell Degranulation ◽  
Negative Regulator ◽  
Kinase C ◽  
Src Homology ◽  
Phosphotyrosine Binding Domain

ABSTRACT Regulation of mast cell degranulation is dependent on the subtle interplay of cellular signaling proteins. The Src homology 2 (SH2) domain-containing inositol-5′-phosphatase (SHIP), which acts as the gatekeeper of degranulation, binds via both its SH2 domain and its phosphorylated NPXY motifs to the adapter protein Shc via the latter's phosphorylated tyrosines and phosphotyrosine-binding domain, respectively. This theoretically leaves Shc's SH2 domain available to bind proteins, which might be part of the SHIP/Shc complex. In a search for such proteins, protein kinase C-δ (PKC-δ) was found to coprecipitate in mast cells with Shc and to interact with Shc's SH2 domain following antigen or pervanadate stimulation. Phosphorylation of PKC-δ's Y332, most likely by Lyn, was found to be responsible for PKC-δ's binding to Shc's SH2 domain. Using PKC-δ−/− bone marrow-derived mast cells (BMMCs), we found that the antigen-induced tyrosine phosphorylation of Shc was similar to that in wild-type (WT) BMMCs while that of SHIP was significantly increased. Moreover, increased translocation of PKC-δ to the membrane, as well as phosphorylation at T505, was observed in SHIP−/− BMMCs, demonstrating that while PKC-δ regulates SHIP phosphorylation, SHIP regulates PKC-δ localization and activation. Interestingly, stimulation of PKC-δ−/− BMMCs with suboptimal doses of antigen yielded a more sustained calcium mobilization and a significantly higher level of degranulation than that of WT cells. Altogether, our data suggest that PKC-δ is a negative regulator of antigen-induced mast cell degranulation.

scholarly journals Calcium- and guanine-nucleotide-dependent exocytosis in permeabilized rat mast cells. Modulation by protein kinase C

1990 ◽  
Vol 265 (2) ◽  
pp. 365-373 ◽  
Author(s):  
W R Koopmann ◽  
R C Jackson
Keyword(s):  
Mast Cell ◽  
Protein Kinase C ◽  
Mast Cells ◽  
Protein Kinase ◽  
Histamine Release ◽  
Cell System ◽  
Peritoneal Mast Cell ◽  
Guanine Nucleotide ◽  
Permeabilized Cell ◽  
Kinase C

We have used a digitonin-permeabilized cell system to study the signal transduction pathways responsible for stimulus-secretion coupling in the rat peritoneal mast cell. Conditions were established for permeabilizing the mast cell plasma membrane without disrupting secretory vesicles. Exocytotic release of histamine from digitonin-permeabilized cells required a combination of micromolar concentrations of Ca2+ and the stable guanine nucleotide analogue guanosine 5′-[gamma-thio]triphosphate (GTP[S]), but was independent of exogenous ATP. In the presence of 40 microM-GTP[S], exocytosis was half-maximal at 1.3 microM-Ca2+ and maximal at 10 microM-Ca2+; GTP[S] alone (100 microM) had no effect on histamine release in the absence of added Ca2+. In the presence of 10 microM free Ca2+, 5 microM-GTP[S] was required for half-maximal exocytosis. To examine the possible role of protein kinase C (PKC) in exocytosis, we utilized 12-O-tetradecanoylphorbol 13-acetate (TPA) to activate PKC and studied its effect on histamine release from permeabilized mast cells. Cells that had been incubated with TPA (25 nM for 5 min) exhibited increased sensitivity to both GTP[S] and Ca2+. The PKC inhibitor staurosporine blocked the effect of TPA without inhibiting normal exocytosis in response to the combination of GTP[S] and Ca2+. In addition, down-regulation of mast-cell PKC by long-term TPA treatment (25 nM for 20 h) blocked the ability of the cells to respond to TPA and inhibited exocytosis in response to Ca2+ and GTP[S] by 40-50%. These results suggest that the sensitivity of the exocytotic machinery of the mast cell can be altered by PKC-catalysed phosphorylation events, but that activation of PKC is not required for exocytosis to occur.

scholarly journals Nanog expression is negatively regulated by protein kinase C activities in human cancer cell lines

2013 ◽  
Vol 34 (7) ◽  
pp. 1497-1509 ◽  
Author(s):  
Wing-Keung Chu ◽  
Pei-Min Dai ◽  
Hsin-Lun Li ◽  
Chia-Chu Pao ◽  
Jan-Kan Chen
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines ◽  
Nanog Expression ◽  
Kinase C

scholarly journals Differential responsiveness of intestinal epithelial cells to 1,25-dihydroxyvitamin D3--role of protein kinase C

2001 ◽  
Vol 169 (1) ◽  
pp. 145-151 ◽  
Author(s):  
HJ Armbrecht ◽  
MA Boltz ◽  
TL Hodam ◽  
VB Kumar
Keyword(s):  
Vitamin D ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Cell Lines ◽  
Phorbol Esters ◽  
Mrna Levels ◽  
Intestinal Epithelial ◽  
Vitamin D Receptors ◽  
Kinase C ◽  
Crypt Cells

Non-transformed rat intestinal epithelial cell (IEC) lines were used to study the action of 1,25-dihydroxyvitamin D(3) (1,25(OH)2D) in the intestine. The capacity of 1,25(OH)2D to increase the expression of the cytochrome P450 component of the vitamin D 24-hydroxylase (CYP24) was determined in IEC-6 and IEC-18 cell lines. In IEC-6 cells, which are derived from crypt cells isolated from the whole small intestine, 1,25(OH)2D markedly increased expression of CYP24 protein and mRNA within 12 h. In contrast, in IEC-18 cells, which are derived from crypt cells from the ileum only, 1,25(OH)2D did not increase expression of CYP24 until 24-48 h. The maximal levels of CYP24 mRNA seen in the IEC-18 cells were only 31% of the maximal levels seen in the IEC-6 cells. In the presence of 1,25(OH)2D, phorbol esters rapidly increased CYP24 mRNA levels in IEC-18 cells from almost undetectable to levels seen in IEC-6 cells. Protein kinase inhibitors abolished the stimulation by 1,25(OH)2D and by phorbol esters in both cell lines. Stimulation of mRNA levels by phorbol esters required new protein synthesis but stimulation by 1,25(OH)2D did not. These studies demonstrated that the rapid action of 1,25(OH)2D in IEC-6 cells is related to the activation of protein kinase C, an event which is missing in the IEC-18 cells. This differential response to 1,25(OH)2D probably takes place at a post-receptor site, since the number of vitamin D receptors in each cell line was found to be similar.

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