Sustained increase in 1,2-diacylglycerol precedes DNA synthesis in epidermal-growth-factor-stimulated fibroblasts. Evidence for stimulated phosphatidylcholine hydrolysis.
A property common to many growth factors is that they must be present for several hours before the commitment to DNA synthesis and cell division occurs. The intracellular signals that are relevant during this period are poorly defined. We examined the formation of 1,2-diacylglycerol in IIC9 fibroblasts after stimulation with epidermal growth factor (EGF), and found that the mass of this lipid remained elevated for at least four hours. The concentration-dependence of EGF-stimulated 1,2-diacylglycerol production and [3H]thymidine incorporation were similar. Studies of phospholipid metabolism strongly suggested that phosphatidylcholine was the source of the 1,2-diacylglycerol generated in response to EGF. EGF did not stimulate the hydrolysis of other phospholipids, including the phosphoinositides, nor did it increase synthesis de novo of 1,2-diacylglycerol. This pattern of sustained 1,2-diacylglycerol formation from phosphatidylcholine may be important in the mitogenic signalling of EGF and potentially other growth factors.
Wright
T M
TM
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Shin
H S
HS
Raben
D M
DM
D000818:Animals; D002460:Cell Line; D002794:Choline / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D004075:Diglycerides / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005989:Glycerides / Q000378:metabolism*; D006868:Hydrolysis; D007700:Kinetics; D010713:Phosphatidylcholines / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism
D004075:Diglycerides; D005989:Glycerides; D010713:Phosphatidylcholines; D010716:Phosphatidylinositols; D004815:Epidermal Growth Factor; D002794:Choline