Involvement of Protein Kinase Cε in the Negative Regulation of Akt Activation Stimulated by Granulocyte Colony-Stimulating Factor

Liu, Hong; Qiu, Yaling; Xiao, Lei; Fan, Daiming

doi:10.4049/jimmunol.176.4.2407

Cited by 16 publications

(17 citation statements)

References 56 publications

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“…Contrary to the data cited above, there are some reports that suggest that PKC negatively regulates Akt function [116][117][118][119][120][121], and this was associated with increased apoptosis. Suppression of Akt phosphorylation in response to PKC activators or adenoviral expression of PKCε has been shown to occur via PP2A [117,119].…”

Section: Pkcε: Akting In Concert To Promote Survivalcontrasting

confidence: 62%

“…Moreover, TPA co-treatment diminished the capacity of IGF to protect against UVC-induced cell death, while PKC inhibitors enhanced cell survival [119]. Similarly, in myeloid cell lines, Liu and colleagues showed that wild-type or constitutively-active PKCε attenuated cell proliferation stimulated by granulocyte colony-stimulating factor [120]. This inhibitory effect was associated with a decrease in Akt phosphorylation.…”

Section: Pkcε: Akting In Concert To Promote Survivalmentioning

confidence: 97%

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Protein kinase Cε makes the life and death decision

Basu

Sivaprasad

2007

Cellular Signalling

144

154

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Cancer is caused by dysregulation in cellular signaling systems that control cell proliferation, differentiation and cell death. Protein kinase C (PKC), a family of serine/threonine kinases, plays an important role in the growth factor signal transduction pathway. PKCε, however, is the only PKC isozyme that has been considered as an oncogene. It can contribute to malignancy by enhancing cell proliferation or by inhibiting cell death. This review focuses on how PKCε collaborates with other signaling pathways, such as Ras/Raf/ERK and Akt, to regulate cell survival and cell death. We have also discussed how PKCε mediates is antiapoptotic signal by altering the level or function of proand antiapoptotic Bcl-2 family members.

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Section: Pkcε: Akting In Concert To Promote Survivalcontrasting

confidence: 62%

Section: Pkcε: Akting In Concert To Promote Survivalmentioning

confidence: 97%

Protein kinase Cε makes the life and death decision

Basu

Sivaprasad

2007

Cellular Signalling

144

154

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“…PI3K products have been shown to activate nPKCε in vitro (35), and IFN␥-induced activation of nPKCε in mesangial cells is inhibited by PI3K inhibitor (7). However, nPKCε and PMA have been shown to inhibit granulocyte colony-stimulating factor-induced activation of PKB in myeloid 32D cells (21), and activation of nPKC␦ and nPKCε results in inhibition of PKB in mouse keratinocytes (20). Thus whether nPKCε regulates PKB activity or PI3K regulates nPKCε activity appears to be dependent on cell type and stimulus.…”

Section: Discussionmentioning

confidence: 99%

“…nPKCε has been shown to inhibit PKB in mouse keratinocytes (20) and myeloid 32D cells (21). Thus we determined whether TLC induced inhibition of PKB in HuH-NTCP cells is mediated via PKCε.…”

Section: Tlc Does Not Inhibit Ntcp Translocation and Competitively Inmentioning

confidence: 99%

“…We studied the effect of a DN-PKCε (HA tagged) to define the role of PKCε. This mutant has been used previously to study the role of nPKCε in other cell types (6,7,21,32). Overexpression of DN-PKCε resulted in several fold increases in PKCε compared with cells transfected with the empty vector (Fig.…”

Section: Tlc Does Not Inhibit Ntcp Translocation and Competitively Inmentioning

confidence: 99%

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PKCε-dependent and -independent effects of taurolithocholate on PI3K/PKB pathway and taurocholate uptake in HuH-NTCP cell line

Schonhoff¹,

Yamazaki²,

Hohenester³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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Schonhoff CM, Yamazaki A, Hohenester S, Webster CRL, Bouscarel B, Anwer MS. PKCε-dependent and -independent effects of taurolithocholate on PI3K/PKB pathway and taurocholate uptake in HuH-NTCP cell line. Am J Physiol Gastrointest Liver Physiol 297: G1259 -G1267, 2009. First published October 8, 2009 doi:10.1152/ajpgi.00177.2009.-The cholestatic bile acid taurolithocholate (TLC) inhibits biliary secretion of organic anions and hepatic uptake of taurocholate (TC). TLC has been suggested to induce retrieval of Mrp2 from the canalicular membrane via the phosphoinositide-3-kinase (PI3K)/PKB-dependent activation of novel protein kinase Cε (nPKCε) in rat hepatocytes. The aim of the present study was to determine whether TLC-induced inhibition of TC uptake may also involve PI3K-dependent activation of PKCε in HuH7 cells stably transfected with human Na ϩ -dependent TC-cotransporting polypeptide (NTCP) (HuH-NTCP cells). To avoid direct competition for uptake, cells were pretreated with TLC, washed, and then incubated with 3 H-TC to determine TC uptake. TLC produced time-and dose-dependent inhibition of TC uptake. TLC inhibited TC uptake competitively without affecting NTCP membrane translocation. A PI3K inhibitor failed to reverse TLC-induced TC uptake inhibition and TLC-inhibited PKB phosphorylation. TLC did activate nPKCε as evidenced by increased membrane translocation and nPKCε-Ser 729 phosphorylation. Overexpression of dominant negative-nPKCε reversed TLC-induced inhibition of PKB phosphorylation but not of TC uptake. Finally, cAMP prevented TLC-induced inhibition of TC uptake via the PI3K pathway, and the prevention is due to the sum of cAMP-induced stimulation and TLC-induced inhibition of TC uptake. Taken together, these results suggest that TLC-induced inhibition of PKB, but not of TC uptake, is mediated via nPKCε. Activation of nPKCε and inhibition of TC uptake by TLC are not mediated via the PI3K/PKB pathway. dominant negative-novel protein kinase Cε; inhibition kinetics; PKB/ Akt; Na ϩ -dependent taurocholate-cotransporting polypeptide; phosphoinositide-3-kinase TRANSHEPATIC TRANSPORT of organic solutes plays an important role in hepatic bile formation, and cholestasis results when hepatic solute transport is inhibited (1). Taurolithocholate (TLC), a secondary bile salt, has been known to produce acute cholestasis by inhibiting biliary secretion of organic anions (18) and has been shown to inhibit taurocholate (TC) uptake in rat hepatocytes (29). The inhibition of biliary organic anion secretion by TLC involves retrieval of Bsep (9) and Mrp2 (2) from the canalicular membrane and may be exacerbated by the inhibition of bile acid uptake. However, the cellular mechanism by which TLC inhibits TC uptake is not known.Hepatic uptake of TC is primarily mediated via Na ϩ -dependent TC-cotransporting polypeptide (NTCP). Cyclic AMP has been shown to stimulate TC uptake by translocating Ntcp to the plasma membrane via phosphoinositide-3-kinase (PI3K) signaling pathway (36,39). Because inhibition of TC uptake by TLC is n...

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Interferon-γ attenuates the survival activity of G-CSF through PI3K/Akt signaling pathway in mouse multipotent progenitor cells

et al. 2007

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Apoptosis plays an important role in the injury to stem and progenitor compartments associated with aberrant interferon-gamma (IFN-gamma) in aplastic anemia (AA), which is characterized by the loss of stem cells; however, its molecular mechanism is poorly understood. In this study, we have addressed the mechanism of the apoptotic function of IFN-gamma against hematopoietic stem and/or progenitors. Although granulocyte colony-stimulating factor (G-CSF) augmented survival and proliferative and differentiating activity in 32D cells, mouse multipotent progenitor cells, these effects were abolished by IFN-gamma and were susceptible to apoptosis with IFN-gamma. IFN-gamma attenuated Akt phosphorylated by G-CSF in a dose- and time-dependent manner. Wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K), enhanced the inhibitory effect on Akt phosphorylated by G-CSF in collaboration with IFN-gamma, suggesting that the activity of IFN-gamma might converge on the PI3K pathway. We examined the expression of Bcl-2-associated death (Bad), which works downstream of Akt. IFN-gamma increased the Bad protein reduced by G-CSF. IFN-gamma induced apoptosis in 32D cells through the caspase pathway. Taken together, these results suggest that IFN-gamma could exert inhibitory action on stem cells and/or progenitors by interference with the PI3K/Akt signaling pathway. Our findings may contribute to understanding the decreased number of stem cells characteristic of AA.

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Involvement of Protein Kinase Cε in the Negative Regulation of Akt Activation Stimulated by Granulocyte Colony-Stimulating Factor

Cited by 16 publications

References 56 publications

Protein kinase Cε makes the life and death decision

Protein kinase Cε makes the life and death decision

PKCε-dependent and -independent effects of taurolithocholate on PI3K/PKB pathway and taurocholate uptake in HuH-NTCP cell line

Interferon-γ attenuates the survival activity of G-CSF through PI3K/Akt signaling pathway in mouse multipotent progenitor cells

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