Antitubulin agents enhance the stimulation of DNA synthesis by polypeptide growth factors in 3T3 mouse fibroblasts.

We have compared the effects of pretreatment of Swiss 3T3 cell with pertussis toxin on the stimulation of DNA synthesis and phosphoinositide hydrolysis in response to a wide variety of mitogens. The toxin substantially inhibited the stimulation of DNA synthesis in response to a phorbol ester or various peptide and polypeptide growth factors irrespective of their ability to activate phosphoinositidase C. Production of inositol phosphates in response to platelet-derived growth factor, fibroblast growth factor and prostaglandin F2 alpha were unaffected by the toxin while bombesin- and vasopressin-stimulated formation of inositol phosphates were inhibited by only 27 and 23% respectively. These results argue against a major role for a pertussis toxin-sensitive G protein in coupling any of these mitogen receptors to activation of a phosphoinositidase C. Furthermore, the results suggest that the widespread inhibitory effects of pertussis toxin on mitogen-stimulated DNA synthesis may be unrelated to the toxin's limited actions on phosphoinositide hydrolysis.

Download Full-text

Late signals are required for the stimulation of DNA synthesis in rat mammary fibroblasts by growth factors

Bioscience Reports ◽

10.1007/bf01207339 ◽

1996 ◽

Vol 16 (3) ◽

pp. 249-263 ◽

Cited By ~ 4

Author(s):

Hai-Lan Chen ◽

Philip S. Rudland ◽

John A. Smith ◽

David G. Fernig

Keyword(s):

Growth Factors ◽

Growth Factor ◽

Dna Synthesis ◽

Maximal Response ◽

High Concentration ◽

Initial Concentration ◽

Maximal Stimulation ◽

Epidermal Growth ◽

Lag Period ◽

Stimulation Of

Maximal stimulation of DNA synthesis in quiescent rat mammary (Rama) 27 fibroblasts is elicited by epidermal growth factor (EGF) or basic fibroblast growth factor (bFGF) 18 h after the initial addition of the growth factors-the ‘lag’ period. At maximally-stimulating concentrations, EGF and bFGF are interchangeable 9 h after their initial addition. When the initial concentration of growth factor is below that required to elicit a maximal response, it is possible to increase the level of DNA synthesis by increasing the concentration of growth factor 9 h after its initial addition. When the initial concentration of growth factor is high, substitution by a lower concentration of growth factor after 9 h allows a greater proportion of cells to synthesize DNA than would be expected from a continuous low dose of growth factor. Similar results are obtained when both the growth factor and its concentration are changed 9 h after the initial addition of growth factor. However, when EGF at a low concentration is substituted for a high concentration of EGF or bFGF the resulting increase in the levels of DNA synthesis is greater when EGF rather than bFGF is added for a second time. The half-life of the growth-stimulatory signals delivered by EGF and by bFGF 9 h after their initial addition is 1–2 h. These results suggest that to stimulate DNA synthesis: (i) EGF or bFGF must deliver a signal(s) continuously; (ii) the initial signals produced by EGF and bFGF are equivalent; (iii) the signals produced between 9–18 h by EGF may be different to those produced by bFGF.

Download Full-text

Growth Factors and Corneal Endothelial Cells: I. Stimulation of Bovine Corneal Endothelial Cell DNA Synthesis by Defined Growth Factors

Cornea ◽

10.1097/00003226-199201000-00001 ◽

1992 ◽

Vol 11 (1) ◽

pp. 1-10 ◽

Cited By ~ 20

Author(s):

Philip G. Woost ◽

Marcia M. Jumblatt ◽

Richard A. Eiferman ◽

Gregory S. Schultz

Keyword(s):

Endothelial Cells ◽

Growth Factors ◽

Endothelial Cell ◽

Dna Synthesis ◽

Corneal Endothelial Cell ◽

Corneal Endothelial Cells ◽

Bovine Corneal Endothelial Cell ◽

Stimulation Of

Download Full-text

Tumor promoter phorbol 12-myristate 13-acetate inhibits mitogen-stimulated Na+/H+ exchange in human epidermoid carcinoma A431 cells.

The Journal of Cell Biology ◽

10.1083/jcb.99.3.1162 ◽

1984 ◽

Vol 99 (3) ◽

pp. 1162-1166 ◽

Cited By ~ 55

Author(s):

B Whiteley ◽

D Cassel ◽

Y X Zhuang ◽

L Glaser

Keyword(s):

Protein Kinase C ◽

Growth Factors ◽

Protein Kinase ◽

Cultured Cells ◽

Tumor Promoter ◽

Hypertonic Solution ◽

A431 Cells ◽

Polypeptide Growth Factors ◽

Kinase C ◽

Stimulation Of

Addition of polypeptide growth factors to cultured cells results in a rapid stimulation of Na+/H+ exchange, which leads to cytoplasmic alkalinization. We studied the effects of the potent tumor promoter phorbol 12-myristate 13-acetate (PMA) on the Na+/H+ exchange system of A431 cells. Stimulation of Na+/H+ exchange by epidermal growth factor (EGF) and serum as well as by vanadate ions is strongly inhibited after treatment of cells with nanomolar concentrations of PMA. Phorbol esters that have no activity as tumor promoters also do not modulate the activation of Na+/H+ exchange. By contrast, the stimulation of Na+/H+ exchange that is produced upon exposure of cells to hypertonic solution is only slightly inhibited by PMA treatment, indicating that PMA treatment does not directly block the activity of the Na+/H+ antiporter. Furthermore, incubation of cells with PMA causes a weak stimulation of Na+/H+ exchange, although this effect is mostly observed at relatively high PMA concentrations and appears to require external Ca2+. The inhibition BY PMA of EGF-promoted Na+/H+ exchange is not due to inhibition of EGF-binding to the EGF receptor. Since PMA activates protein kinase C, our observations are consistent with the hypothesis that protein kinase C functions to attenuate the stimulation of Na+/H+ exchange by polypeptide growth factors.

Download Full-text