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dc.contributor.authorWhetton, Anthony D
dc.contributor.authorMonk, P N
dc.contributor.authorConsalvey, S D
dc.contributor.authorHuang, S J
dc.contributor.authorDexter, T Michael
dc.contributor.authorDownes, C P
dc.date.accessioned2010-11-11T16:20:48Z
dc.date.available2010-11-11T16:20:48Z
dc.date.issued1988-05
dc.identifier.citationInterleukin 3 stimulates proliferation via protein kinase C activation without increasing inositol lipid turnover. 1988, 85 (10):3284-8 Proc Natl Acad Sci USAen
dc.identifier.issn0027-8424
dc.identifier.pmid3259317
dc.identifier.urihttp://hdl.handle.net/10541/115443
dc.description.abstractInterleukin 3 (IL-3) is required for the survival and proliferation of the FDCP-Mix 1 multipotent stem cell line. IL-3 or phorbol esters can rapidly translocate protein kinase C from a cytosolic to a membrane-bound form in these cells. Phorbol esters were able to partially replace the requirement of FDCP-Mix 1 cells for IL-3. Down-modulation of protein kinase C levels by chronic treatment with phorbol ester markedly reduced the ability of the cells to proliferate in response to either IL-3 or phorbol esters. These data indicate that IL-3 can activate protein kinase C, leading to the survival and proliferation of stem cells. Protein kinase C is activated conventionally by complexing with diacylglycerol which accumulates in the cell membrane after agonist-stimulated hydrolysis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2]. However, there was no detectable breakdown of PtdIns(4,5)P2 when IL-3 was added to FDCP-Mix 1 cells, nor was there detectable accumulation of inositol phosphates in response to IL-3. In contrast, rapid hydrolysis of PtdIns(4,5)P2 and accumulation of inositol 1,4,5-trisphosphate was elicited by readdition of horse serum to serum-starved cells, thus indicating that these cells possess the necessary machinery to undergo agonist-mediated inositol phospholipid breakdown. We conclude that the mechanism whereby IL-3 can activate protein kinase C leading to proliferation is not associated with inositol phospholipid hydrolysis.
dc.language.isoenen
dc.subject.meshCaenorhabditis elegans Proteins
dc.subject.meshCalcium
dc.subject.meshCarcinogens
dc.subject.meshCell Line
dc.subject.meshCell Survival
dc.subject.meshDNA Replication
dc.subject.meshEnzyme Activation
dc.subject.meshInositol
dc.subject.meshInterleukin-3
dc.subject.meshPhorbol 12,13-Dibutyrate
dc.subject.meshPhorbol Esters
dc.subject.meshPhosphatidylinositols
dc.subject.meshProtein Kinase C
dc.subject.meshReceptors, Drug
dc.subject.meshTetradecanoylphorbol Acetate
dc.titleInterleukin 3 stimulates proliferation via protein kinase C activation without increasing inositol lipid turnover.en
dc.typeArticleen
dc.contributor.departmentDepartment of Biochemistry and Applied Molecular Biology, UMIST, Manchester, United Kingdom.en
dc.identifier.journalProceedings of the National Academy of Sciences of the United States of Americaen
html.description.abstractInterleukin 3 (IL-3) is required for the survival and proliferation of the FDCP-Mix 1 multipotent stem cell line. IL-3 or phorbol esters can rapidly translocate protein kinase C from a cytosolic to a membrane-bound form in these cells. Phorbol esters were able to partially replace the requirement of FDCP-Mix 1 cells for IL-3. Down-modulation of protein kinase C levels by chronic treatment with phorbol ester markedly reduced the ability of the cells to proliferate in response to either IL-3 or phorbol esters. These data indicate that IL-3 can activate protein kinase C, leading to the survival and proliferation of stem cells. Protein kinase C is activated conventionally by complexing with diacylglycerol which accumulates in the cell membrane after agonist-stimulated hydrolysis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2]. However, there was no detectable breakdown of PtdIns(4,5)P2 when IL-3 was added to FDCP-Mix 1 cells, nor was there detectable accumulation of inositol phosphates in response to IL-3. In contrast, rapid hydrolysis of PtdIns(4,5)P2 and accumulation of inositol 1,4,5-trisphosphate was elicited by readdition of horse serum to serum-starved cells, thus indicating that these cells possess the necessary machinery to undergo agonist-mediated inositol phospholipid breakdown. We conclude that the mechanism whereby IL-3 can activate protein kinase C leading to proliferation is not associated with inositol phospholipid hydrolysis.


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