Protein kinase Cδ functions downstream of Ca2+ mobilization in FcεRI signaling to degranulation in mast cells

Cho, Sung Hoon; Woo, Chang Hoon; Yoon, Seog Beom; Kim, Jae Hong

doi:10.1016/j.jaci.2004.07.035

Cited by 63 publications

(52 citation statements)

References 36 publications

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“…The Ca influx causes the translocation of PKC from cytosol to the membrane and enhances its activity. 35,36) The fusion proteins synaptosome-associated protein(SNAP)-23, SNAP25 and syntaxin4 are target for PKC-mediated phosphorylation, suggesting that PKC might play a role in the terminal granule mobilization and membrane fusion events associated with the degranulation process. 37) With respect to PKC, there are eleven isozymes of PKC which are classified in three families, the classical PKCs (a, bI, bII and g), the novel PKCs (d, e, q and h) and the atypical PKCs (z, i/l) according to the dependence of both DAG and Ca 2ϩ , only DAG and neither DAG nor Ca 2ϩ , respectively.…”

Section: Discussionmentioning

confidence: 99%

Effects of Benzylidenecyclopentanone Analogues of Curcumin on Histamine Release from Mast Cells

2009

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Curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] is a natural yellow pigment isolated from the rhizomes of the plant Curcuma longa L. (turmeric). Its chemical structure is described in Fig. 1.1) The pharmacological effects of curcumin include anti-inflammatory, 2) antioxidant, 3) antiprotozoal, 4) antibacterial, 5) anticancer, 6) antihepatotoxic, 7) hypolipidemic, 8) and antifibrotic effects. 9) Curcumin showed no toxicity in acute toxicity studies in rats, guinea pigs, and monkeys, 10) as well as in humans. 11)Several prior studies have examined the effects of curcumin on allergic diseases. An ethyl acetate extract of Curcuma longa L., which contains curcuminnoids, exhibited a preventive effect in allergic type I and IV models.12) Furthermore, both the ethyl acetate extract of Curcuma longa L. and curcumin were found to decrease histamine release from mast cells. However the ethyl acetate extract of Curcuma longa L. had somewhat stronger activity than that of curcumin, which may have been due to the presence of curcumin derivatives.13) Several studies have also examined the anti-allergic activity of curcumin and curcumin-related compounds in relation to their antioxidant effects. Most of these compounds were shown to inhibit histamine release from rat basophilic leukemia (RBL-2H3) cells; however, histamine release was decreased by antioxidant compounds and by those that lacked antioxidant activity. The results suggested that the hydroxy moiety of curcumin is responsible for antioxidant activity and may also contribute to the inhibition of histamine release. 14) In a guinea pig model of airway hyperresponsiveness, curcumin at a dose of 20 mg/kg body weight significantly inhibited ovalbumin (OVA)-induced airway constriction and airway hyperactivity. 15)Although curcumin has a wide range of potentially beneficial pharmacological effects, its use is limited by the compounds instability. The stability of curcumin is strongly affected by factors such as pH and exposure to light.16) The kinetics of the pH-dependent degradation of curcumin in aqueous medium at various pH levels was studied by Tonnesen and Karlsen. 17) They found that curcumin in aqueous solution at pH less than 7 is quite stable, but with increasing pH, curcumin decomposes. The main decomposition products are ferulic acid and feruloylmethane, which rapidly undergo retro-aldol condensation to vanillin and acetone. The instability of curcumin at alkaline pH is caused by the active methylene moiety. Decomposition of curcumin can also occur as a result of light exposure, and this process is also mediated by the active methylene moiety; the degradation products include ferulic aldehyde, ferulic acid, dihydroxynaphthalene product, 4-vinylguaiacol, vanillin, and vanillic acid. 16,17) The modification of the middle site of curcumin to compounds such as the 1,4-pentadiene-3-ones, cyclopentanone, and cyclohexanone which lack the active methylene moiety and one carbonyl moiety of curcumin may show improved stability. These compounds which st...

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Section: Discussionmentioning

confidence: 99%

Effects of Benzylidenecyclopentanone Analogues of Curcumin on Histamine Release from Mast Cells

2009

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“…In that study, carbachol-stimulated insulin secretion was not reduced by Go6976 but was significantly suppressed by an ambiguous PKC inhibitor, chelerythrine, suggesting that a novel PKC isoform, ␦ or , might play a regulatory role in the process. Cho et al 17 demonstrated that PKC␦ activation is involved in antigen-induced mast cell degranulation, which could subsequently be inhibited by rottlerin or transfection of a dominant-negative mutant of PKC␦. In contrast, Leitges et al 16 reported that PKC␦ is a negative regulator of antigen-induced mast cell degranulation.…”

Section: Discussionmentioning

confidence: 99%

“…[12][13][14] Increasing evidence suggests that PKC␦ mediates exocytotic secretion in several different cell types. 4,8,[15][16][17] Supported by Grant R37 HL36982 from the NIH.…”

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confidence: 99%

Protein Kinase Cδ Regulates Airway Mucin Secretion via Phosphorylation of MARCKS Protein

Park

Crews

Lampe

et al. 2007

The American Journal of Pathology

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“…Fc⑀RI aggregation results in downstream signals that include the activation of several members of the protein kinase C family (14,42), which leads to degradation of the B inhibitor allowing the nuclear translocation of NFB (43). Using a similar strategy as the study of NFAT activation, we transiently transfected wildtype or Syk mutants into stably transfected Syk-negative NFB-GFP reporter cells.…”

Section: Conserved Tyrosines Of Syk Cooh-terminal Region Are Requiredmentioning

confidence: 99%

Tyrosines in the Carboxyl Terminus Regulate Syk Kinase Activity and Function

Castro

Zhang

Jamur

et al. 2010

Journal of Biological Chemistry

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The Syk tyrosine kinase family plays an essential role in immunoreceptor tyrosine-based activation motif (ITAM) signaling. The binding of Syk to tyrosine-phosphorylated ITAM subunits of immunoreceptors, such as Fc⑀RI on mast cells, results in a conformational change, with an increase of enzymatic activity of Syk. This conformational change exposes the COOH-terminal tail of Syk, which has three conserved Tyr residues (Tyr-623, Tyr-624, and Tyr-625 of rat Syk). To understand the role of these residues in signaling, wild-type and mutant Syk with these three Tyr mutated to Phe was expressed in Syk-deficient mast cells. There was decreased Fc⑀RI-induced degranulation, nuclear factor for T cell activation and NFB activation with the mutated Syk together with reduced phosphorylation of MAP kinases p38 and p42/44 ERK. In non-stimulated cells, the mutated Syk was more tyrosine phosphorylated predominantly as a result of autophosphorylation. In vitro, there was reduced binding of mutated Syk to phosphorylated ITAM due to this increased phosphorylation. This mutated Syk from non-stimulated cells had significantly reduced kinase activity toward an exogenous substrate, whereas its autophosphorylation capacity was not affected. However, the kinase activity and the autophosphorylation capacity of this mutated Syk were dramatically decreased when the protein was dephosphorylated before the in vitro kinase reaction. Furthermore, mutation of these tyrosines in the COOH-terminal region of Syk transforms it to an enzyme, similar to its homolog ZAP-70, which depends on other tyrosine kinases for optimal activation. In testing Syk mutated singly at each one of the tyrosines, Tyr-624 but especially Tyr-625 had the major role in these reactions. Therefore, these results indicate that these tyrosines in the tail region play a critical role in regulating the kinase activity and function of Syk.Syk and ZAP-70 are members of a tyrosine kinase family one or both of which are expressed in most hematopoietic cells (1-5). Structurally Syk/ZAP-70 consists of two Src-homology 2 domains (SH2) 3 and a kinase domain followed by a short COOH-terminal extension (tail). The inter-SH2 domain is located between the NH 2 -terminal SH2 (SH2-N) and COOHterminal SH2 (SH2-C), whereas the linker region is between the SH2-C and the kinase domains (6, 7). An alternatively spliced form of Syk, termed SykB, lacks a 23-amino acid sequence in the linker domain (8). Although both isoforms are expressed in immune cells such as the RBL-2H3 rat mast cell line, Syk is more efficient than SykB in immunoreceptor signaling (8,9). Syk is expressed in B cells, mast cells, immature T cells, and platelets, whereas ZAP-70 is in T cells and natural killer cells (3, 10). Syk and ZAP-70 are essential for signal transduction from cell surface immunoreceptors (10 -12). These receptors on many hematopoietic cells such as T, B, and mast cells have subunits, which contain a sequence named the immunoreceptor tyrosine-based activation motif (ITAM) which contains two tyrosine residues (13...

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Protein kinase Cδ functions downstream of Ca2+ mobilization in FcεRI signaling to degranulation in mast cells

Cited by 63 publications

References 36 publications

Effects of Benzylidenecyclopentanone Analogues of Curcumin on Histamine Release from Mast Cells

Effects of Benzylidenecyclopentanone Analogues of Curcumin on Histamine Release from Mast Cells

Protein Kinase Cδ Regulates Airway Mucin Secretion via Phosphorylation of MARCKS Protein

Tyrosines in the Carboxyl Terminus Regulate Syk Kinase Activity and Function

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