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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2008.1
- 수록면
- 39 - 44 (6page)
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Purpose: We investigated the molecular mechanism by
which the Raf-1 kinase pathways that are linked to protein
kinase C induce differential physiological effects, depending
on the stimulus, by employing the pharmacological
PKC activator PMA.
Materials and Methods: Parental and v-Ha-ras transfected
NIH 3T3 cells were chosen as test systems and
these cells were transiently transfected with the pMTH
vector that encodes dominant-negative (DN) PKC-ε
with using Lipofectamine 2000. The cell proliferation reagent
WST-1 was used for the quantitative determination
of cellular proliferation. The Raf-1 kinase activity was
measured by assessing the phosphorylation of recombinant
MEK with using the immunoprecipitated Raf-1
proteins. The phosphorylated MEK protein bands were
quantified by using Quantity One analysis software.
Results: The pharmacological PKC activator phorbol-
12-myristate-13-acetate (PMA) and platelet-derived
growth factor (PDGF) were able to induce the activation of
Raf-1 kinase in the v-H-ras-transformed NIH3T3 fibroblasts.
However, PMA was found to be much less sensitive
PI3 kinase inhibitor or the chemical antioxidant than is
PDGF. Especially, PMA mediated growth arrest while
PDGF induced mitogenic signaling through the PKC-ε
activation. Thus, the regulation of the Raf-1 cascade by
both PDGF and PMA is likely to be intimately linked and
they converge at the PKC level through different upstream
pathways, as was shown by the inhibition of
PDGF-induced Raf-1 kinase activation by the transient
transfection with a dominant-negative mutant of PKC-ε.
Conclusions: Taken together, these results imply that,
depending on the stimulus, Raf-1 kinase leads to different
physiological effects.
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참고문헌 (23)
참고문헌 신청
Arcaro A. / 1993 / Wortmannin is a potent phosphatidylinositol 3-kinase inhibitor: the role of phosphatidylinositol 3,4,5-trisphosphate in neutrophil responses / Biochem J 2
Blobe GC / 1996 / Protein kinase C isoenzymes: regulation and function / Cancer Surv 27 : 213 ~ 48
Cai H. / 1997 / Role of diacylglycerol-regulated protein kinase C isotypes in growth factor activation of the Raf-1 protein kinase / Mol Cell Biol 17 : 732 ~ 41
Corbit KC / 2003 / Activation of Raf-1 signaling by protein kinase C through a mechanism involving Raf kinase inhibitory protein / J Biol Chem 278 : 13061 ~ 68
Dhillon AS / 2007 / Phosphatase and feedback regulation of Raf-1 signaling / Cell Cycle 6 : 3 ~ 7
Blobe GC / 1996 / Protein kinase C isoenzymes: regulation and function / Cancer Surv 27 : 213 ~ 48
Cai H. / 1997 / Role of diacylglycerol-regulated protein kinase C isotypes in growth factor activation of the Raf-1 protein kinase / Mol Cell Biol 17 : 732 ~ 41
Corbit KC / 2003 / Activation of Raf-1 signaling by protein kinase C through a mechanism involving Raf kinase inhibitory protein / J Biol Chem 278 : 13061 ~ 68
Dhillon AS / 2007 / Phosphatase and feedback regulation of Raf-1 signaling / Cell Cycle 6 : 3 ~ 7
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