Phosphoinositide turnover in cell growth and transformation

Thesis/Dissertation · Thu Jan 01 00:00:00 EST 1987

OSTI ID:6583184

Fleischman, L F

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
• Resource Relation: Other Information: Thesis (Ph. D.)
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
MEMBRANE PROTEINS
METABOLISM
ONCOGENIC TRANSFORMATIONS
BIOLOGICAL PATHWAYS
CELL CYCLE
GLYCEROL
INOSITOL
LIPASE
PHOSPHATES
PHOSPHOLIPIDS
PHOSPHORYLATION
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TUMOR CELLS
ALCOHOLS
ANIMAL CELLS
CARBOHYDRATES
CARBOXYLESTERASES
CELL TRANSFORMATIONS
CHEMICAL REACTIONS
ENZYMES
ESTERASES
ESTERS
HYDROLASES
HYDROXY COMPOUNDS
INOSITOLS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIPIDS
MONOSACCHARIDES
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
OXYGEN COMPOUNDS
PHOSPHORUS COMPOUNDS
PROTEINS
SACCHARIDES
550201* - Biochemistry- Tracer Techniques