Synthesis of diacylglycerol de novo is responsible for permanent activation and down-regulation of protein kinase C in transformed cells

Journal Article · Tue Oct 31 00:00:00 EST 1989 · Biochemical and Biophysical Research Communications; (USA)

DOI:https://doi.org/10.1016/0006-291X(89)91532-5· OSTI ID:5026814

Chiarugi, V; Bruni, P; Pasquali, F; Magnelli, L; Basi, G; Ruggiero, M; Farnararo, M ^[1]

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1. Univ. of Firenze (Italy)

We measured the synthesis of diacylglycerol de novo in normal NIH/3T3 fibroblasts and in cells transformed by ras, src, sis and abl oncogenes. Analysis of the incorporation of glucose-derived {sup 14}C into diacylglycerol indicated that neosynthesis of diacylglycerol was constitutively active in the transformed cell lines. Elevated levels of diacylglycerol and persistent activation/down-regulation of protein kinase C reduced the binding of phorbol dibutyrate to transformed cells. This phenomenon could be reversed by blocking the glycolytic pathway, thus indicating that neosynthesized diacylglycerol was responsible for persistent activation and down-regulation of protein kinase C. In transformed cells, protein kinase C activity could not be stimulated by the addition of diolein; however, inhibition of glycolysis restored the ability of transformed cells to respond to diolein. Taken together these data indicate that constitutive synthesis of diacylglycerol de novo is responsible for activation and down-regulation of protein kinase C in transformed cells, and it may play a role in altered mitogenic signalling.

• OSTI ID: 5026814
• Journal Information: Biochemical and Biophysical Research Communications; (USA), Vol. 164:2; ISSN 0006-291X
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
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PHOSPHOTRANSFERASES
ENZYME ACTIVITY
BIOLOGICAL PATHWAYS
CARBON 14 COMPOUNDS
FIBROBLASTS
MICE
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MAMMALS
MEMBRANE PROTEINS
MONOSACCHARIDES
ORGANIC COMPOUNDS
PHOSPHORUS-GROUP TRANSFERASES
PROTEINS
RODENTS
SACCHARIDES
SOMATIC CELLS
SYNTHESIS
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550201* - Biochemistry- Tracer Techniques