Phosphoinositide turnover in cell growth and transformation
Interaction of cells with various stimuli triggers a common signal transduction pathway involving breakdown and resynthesis of the minor membrane lipid phosphatidylinositol-4,5-bisphosphate (PIP/sub 2/). Hydrolysis of PIP/sub 2/ by phospholipase C generates two key catabolites-inositol-1,4,5-trisphosphate (IP/sub 3/) and diacylglycerol (DAG)-which mediate and amplify cellular responses. These studies provide evidence for potential involvement of this pathway in oncogenic transformation and cell cycle progression. Altered levels of PIP/sub 2/ and its breakdown products were found in cells transformed by ras oncogenes, in contrast to untransformed counterparts. Steady-state levels of PIP/sub 2/, DAG and inositol phosphates were measured in NIH 3T3 and NRK cells metabolically labelled with /sup 3/H-glycerol and /sup 3/H-inositol. DAG and inositol phosphate levels were significantly elevated by 2.5-3 fold in the transformed cells while levels of PIP/sub 2/ were decreased. These findings suggest that the ras protein may activate phospholipase C. Elevated DAG content in the transformed cells was also measured by phosphorylation of DAG using a partially purified DAG kinase, indicating that the differences seen could not be attributed to differences in labelling between the cell lines.
- Research Organization:
- Harvard Univ., Boston, MA (USA)
- OSTI ID:
- 6583184
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ALCOHOLS
ANIMAL CELLS
BIOLOGICAL PATHWAYS
CARBOHYDRATES
CARBOXYLESTERASES
CELL CYCLE
CELL TRANSFORMATIONS
CHEMICAL REACTIONS
ENZYMES
ESTERASES
ESTERS
GLYCEROL
HYDROLASES
HYDROXY COMPOUNDS
INOSITOL
INOSITOLS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIPASE
LIPIDS
MEMBRANE PROTEINS
METABOLISM
MONOSACCHARIDES
ONCOGENIC TRANSFORMATIONS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
OXYGEN COMPOUNDS
PHOSPHATES
PHOSPHOLIPIDS
PHOSPHORUS COMPOUNDS
PHOSPHORYLATION
PROTEINS
SACCHARIDES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TUMOR CELLS