scholarly journals Sustained increase in 1,2-diacylglycerol precedes DNA synthesis in epidermal-growth-factor-stimulated fibroblasts. Evidence for stimulated phosphatidylcholine hydrolysis

1990 ◽  
Vol 267 (2) ◽  
pp. 501-507 ◽  
Author(s):  
T M Wright ◽  
H S Shin ◽  
D M Raben
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Dna Synthesis ◽  
De Novo ◽  
Phospholipid Metabolism ◽  
Intracellular Signals ◽  
Mitogenic Signalling ◽  
Epidermal Growth ◽  
Hydrolysis Of

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.

scholarly journals Role of the Different Mitogen-Activated Protein Kinase Subfamilies in the Stimulation of Dog and Human Thyroid Epithelial Cell Proliferation by Cyclic Adenosine 5′-Monophosphate and Growth Factors

Endocrinology ◽  
2003 ◽  
Vol 144 (4) ◽  
pp. 1341-1349 ◽  
Author(s):  
Fabrice Vandeput ◽  
Sandrine Perpete ◽  
Katia Coulonval ◽  
Françoise Lamy ◽  
Jacques E. Dumont
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Protein Kinase ◽  
Epidermal Growth Factor ◽  
Dna Synthesis ◽  
P38 Mapk ◽  
Primary Cultures ◽  
Human Thyroid ◽  
Epidermal Growth

Abstract We have investigated the role of the different classes of MAPKs, i.e. ERKs, c-Jun N-terminal kinases (JNKs), and p38 MAPK in the proliferation of dog and human thyroid epithelial cells (thyrocytes) in primary cultures. In these cells, TSH, acting through cAMP, epidermal growth factor, hepatocyte growth factor (HGF), and phorbol 12-myristate 13-acetate induce DNA synthesis. With the exception of HGF, all of these factors require the presence of insulin for mitogenic effects to be expressed. We found that TSH and forskolin are without effect on the phosphorylation and activity of the different classes of MAPKs. In contrast, all the cAMP-independent growth factors, whereas without effect on the phosphorylation and activity of JNKs and p38 MAPK, stimulated the ERKs. This effect was strong and sustained in response to HGF, epidermal growth factor and 12-myristate 13-acetate but weak and transient in response to insulin. Moreover, whereas in stimulated cells DNA synthesis was inhibited by PD 098059, an inhibitor of MAPK kinase 1 and consequently of ERKs, it was not modified by SB 203580, an inhibitor of p38 MAPK. Taken together, these data 1) exclude a role of JNKs and p38 MAPK in the proliferation of dog and human thyrocytes; 2) suggest that the mitogenic action of the cAMP-independent agents requires a strong and sustained activation of both ERKs and phosphatidylinositol 3-kinase/protein kinase B as realized by HGF alone or by the other agents together with insulin; and 3) show that TSH and cAMP do not activate ERKs but that the weak activation of ERKs by insulin is nevertheless necessary for DNA synthesis to occur.

Insulin and epidermal growth factor are growth factors for isolated porcine thyroid follicles

1985 ◽  
Vol 110 (1_Suppla) ◽  
pp. S74
Author(s):  
R. GÄRTNER ◽  
W. GREIL ◽  
R. DEMHARTER ◽  
K. HORN
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Epidermal Growth

Aging: altered responsiveness of gastric mucosa to epidermal growth factor

1989 ◽  
Vol 257 (4) ◽  
pp. G554-G560 ◽  
Author(s):  
A. P. Majumdar ◽  
F. L. Arlow
Keyword(s):  
Growth Factor ◽  
Gastric Mucosa ◽  
Epidermal Growth Factor ◽  
Dna Synthesis ◽  
Thymidine Kinase ◽  
Membrane Fraction ◽  
Kinase Activity ◽  
Thymidine Kinase Activity ◽  
Epidermal Growth ◽  
K Activity

The present investigation examines the responsiveness of the gastric mucosa to the growth-promoting action of epidermal growth factor (EGF) during advancing age. Two sets of experiments were performed. In the first set of experiments, groups of 4-, 8-, 16-, and 24-mo-old Fischer 344 rats were injected subcutaneously at 12-h intervals for 2 days with either EGF (10 micrograms/kg) in gelatin or the vehicle only (controls). The animals were killed 16-18 h after the last injection. The oxyntic gland mucosa was assayed for thymidine kinase and the rate of DNA synthesis in vitro (indicators of proliferative activity) as well as for tyrosine kinase (Tyr-k) activity. In control rats, the rate of DNA synthesis and thymidine kinase activity rose steadily between 4 and 24 mo of age. However, whereas Tyr-k activity in the gastric mucosal cytosol changed only marginally with age, activity of the enzyme in the membrane fraction rose steadily between 4 and 16 mo and then increased abruptly. EGF stimulated gastric mucosal DNA synthesis and thymidine kinase activity in 4- to 16-mo-old rats compared with the corresponding controls, but in the 24-mo-old animals, it caused a significant 40-50% inhibition. EGF had no demonstrable effect on Tyr-k activity in either cytosolic or membrane fraction. We postulated that Tyr-k activity might have returned to basal level 16-18 h after the last EGF injection.(ABSTRACT TRUNCATED AT 250 WORDS)

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