Phorbol esters modulate the turnover of both ether- and ester-linked phospholipids in cultured mammalian cells

Hii, Charles S.; Kokke, Yasmin S.; Clark, Katherine J.; Murray, Andrew W.

doi:10.1016/0167-4889(90)90229-7

Cited by 15 publications

(5 citation statements)

References 25 publications

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“…Initially, this leads to the formation of benign skin tumors (papillomas) followed by progression to malignant SCCs. Early studies searching for the molecular targets of chemical carcinogenesis revealed that phorbol esters are in fact broad-spectrum activators of the classical and novel PKC isoforms (Hansen et al 1990;Hecker 1985;Hii et al 1990;Imamoto et al 1993;Krauter et al 1996;Mills et al 1993). Short TPA exposure induces PKC activation accompanied by translocation of PKC isoforms from the cytosol to membrane or cytoskeletal compartments.…”

Section: Role Of Speciwc Pkc Isoforms In Skin Tumorigenesismentioning

confidence: 98%

“…The common twostep protocol in chemical carcinogenesis is based on an initiation step, using a low dose of the carcinogen DMBA, and a subsequent promotion phase with repeated applications of a tumor promoter, usually the phorbol ester TPA (Hecker 1985;Hii et al 1990;Mills and Smart 1989; for a recent comprehensive review: Griner and Kazanietz 2007). Initially, this leads to the formation of benign skin tumors (papillomas) followed by progression to malignant SCCs.…”

Section: Role Of Speciwc Pkc Isoforms In Skin Tumorigenesismentioning

confidence: 99%

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Protein kinase C family: On the crossroads of cell signaling in skin and tumor epithelium

Breitkreutz

Braiman-Wiksman²,

Daum

et al. 2007

J Cancer Res Clin Oncol

127

121

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The protein kinase C (PKC) family represents a large group of phospholipid dependent enzymes catalyzing the covalent transfer of phosphate from ATP to serine and threonine residues of proteins. Phosphorylation of the substrate proteins induces a conformational change resulting in modification of their functional properties. The PKC family consists of at least ten members, divided into three subgroups: classical PKCs (alpha, betaI, betaII, gamma), novel PKCs (delta, epsilon, eta, theta), and atypical PKCs (zeta, iota/lambda). The specific cofactor requirements, tissue distribution, and cellular compartmentalization suggest differential functions and fine tuning of specific signaling cascades for each isoform. Thus, specific stimuli can lead to differential responses via isoform specific PKC signaling regulated by their expression, localization, and phosphorylation status in particular biological settings. PKC isoforms are activated by a variety of extracellular signals and, in turn, modify the activities of cellular proteins including receptors, enzymes, cytoskeletal proteins, and transcription factors. Accordingly, the PKC family plays a central role in cellular signal processing. Accumulating data suggest that various PKC isoforms participate in the regulation of cell proliferation, differentiation, survival and death. These findings have enabled identification of abnormalities in PKC isoform function, as they occur in several cancers. Specifically, the initiation of squamous cell carcinoma formation and progression to the malignant phenotype was found to be associated with distinct changes in PKC expression, activation, distribution, and phosphorylation. These studies were recently further extended to transgenic and knockout animals, which allowed a more direct analysis of individual PKC functions. Accordingly, this review is focused on the involvement of PKC in physiology and pathology of the skin.

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Section: Role Of Speciwc Pkc Isoforms In Skin Tumorigenesismentioning

confidence: 98%

Section: Role Of Speciwc Pkc Isoforms In Skin Tumorigenesismentioning

confidence: 99%

Protein kinase C family: On the crossroads of cell signaling in skin and tumor epithelium

Breitkreutz

Braiman-Wiksman²,

Daum

et al. 2007

J Cancer Res Clin Oncol

127

121

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“…Several groups have shown that tumor promoters stimulate the incorporation of choline [11,13] and ethanolamine [4] into membrane phospholipids.…”

Section: Discussionmentioning

confidence: 99%

Possible involvement of the base exchange enzymes in the phospholipid metabolism in LAN-2 cells

Sorrentino

Singh

Massarelli³

et al. 1993

Ital J Neuro Sci

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The incorporation of [14C] choline, [14C] ethanolamine, and [14C] serine by LAN-2 cells into their corresponding phospholipids was investigated in the presence or absence of TPA. The presence of TPA increased the amount of radioactivity incorporated into the phospholipids with a corresponding decrease in the amount of radioactivity in the cytosolic compartment compared to control cultures. There were no differences between TPA-exposed and control cells in the distribution of radioactivity in free choline, phosphorylcholine or CDP-choline of [14C] choline labeled cells. This indicates that the increased lipid labeling was not accompanied by enhanced labeling of the intermediates of the de novo pathway. These results suggest that a choline base exchange enzyme was stimulated in TPA exposed cells. In addition, the enhanced incorporation of serine by TPA into its corresponding phospholipid implies the stimulation of the serine base exchange enzyme which is responsible for phosphatidylserine synthesis in mammals. These observations suggest a

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“…5 ) into their corresponding phospholipids but reduced the incorporation into the hydrophilic compounds. Several investigators have shown that tumor promotors stimulated the incorporation of choline (Lijian et al, 1988;Nishino et al, 1983;Sakamoto et al, 1981) and ethanolamine (Hii et al, 1990) into membrane phospholipids. Our results indicate that the TPA-enhanced incorporation of [ 14C]choline and [ ''C]ethanolamine also applies to ['4C]~erine with these LA-N-2 cells.…”

Section: Discussionmentioning

confidence: 99%

“…Although less extensively investigated, there are suggestions that TPA has similar influence on phosphatidylethanolamine metabolism (Hii et al, 1990;Kiss and Anderson, 1989). Even less is known about effects, if any, upon the metabolism of phosphatidylserine.…”

Section: Introductionmentioning

confidence: 99%

Phorbol esters modulate phospholipid metabolism in a human cholinergic cell line, LA‐N‐2: A possible role for the base exchange enzymes

Singh

McCartney

Sorrentino

et al. 1992

J of Neuroscience Research

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It was shown that in LA-N-2 cells prelabeled with [3H-methyl]choline for 24 hr (Singh et al.: Mol Chem Neuropathol 14:53-66, 1991) the major intracellular and extracellular hydrophilic compound was phosphorylcholine. LA-N-2 cells were labeled with [14C-methyl]choline for 24 hr, harvested, and incubated in Hepes/BSA/saline buffer for varying periods of time. The radioactive compound present in the cytosol and released into Hepes/BSA/saline buffer medium in the presence or absence of TPA was phosphorylcholine. There was a gradual increase in the appearance of radioactivity in the medium and this corresponded to a gradual decline in the radioactivity present in the cytosolic compartment with a statistically significant P value of less than .005. Identical results were obtained with prelabeled cells subsequently incubated with TPA. There was no significant change in the amount of radioactivity associated with lipid suggesting that the phosphorylcholine may be released directly from the cytosolic compartment into the medium rather than originating through a phospholipase-C catalyzed hydrolysis of phosphatidylcholine. This possibility received support from experiments in which cells were electropermeabilized in the presence of radioactive phosphorylcholine. It was found that the introduced [14C]phosphorylcholine was released intact into the incubation medium from the cytosolic compartment. The incorporation of [14C]choline, [14C]ethanolamine, and [14C]serine by LA-N-2 cells into their corresponding phospholipids was investigated in the presence or absence of TPA. The presence of TPA increased the amount of radioactivity incorporated into the phospholipids with a corresponding decrease in the amount of radioactivity in the cytosolic compartment compared to control cultures. There were no detectable differences between TPA exposed and control cells in the distribution of radioactivity in free choline, phosphorylcholine, or CDP-choline of [14C] choline labeled cells. This indicates that the increased lipid labeling was not accompanied by enhanced labeling of the intermediates of the de novo pathway. This effect of TPA in altering the distribution of labeling of the cytosolic and lipid components was not demonstrable with cells grown in the presence of 10(-5) M retinoic acid.

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Phorbol esters modulate the turnover of both ether- and ester-linked phospholipids in cultured mammalian cells

Cited by 15 publications

References 25 publications

Protein kinase C family: On the crossroads of cell signaling in skin and tumor epithelium

Protein kinase C family: On the crossroads of cell signaling in skin and tumor epithelium

Possible involvement of the base exchange enzymes in the phospholipid metabolism in LAN-2 cells

Phorbol esters modulate phospholipid metabolism in a human cholinergic cell line, LA‐N‐2: A possible role for the base exchange enzymes

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