TY - JOUR
T1 - Effects of EGF and thrombin on inositol‐containing phospholipids of cultured fibroblasts
T2 - Stimulation of phosphatidylinositol synthesis by thrombin but not EGF
AU - Raben, Daniel M.
AU - Cunningham, Dennis D.
PY - 1985/12
Y1 - 1985/12
N2 - The effects of growth factors on inositol‐containing phospholipids were investigated to test the hypothesis that alterations in their metabolism are involved in mitogenic stimulation. Thrombin and EGF stimulated comparable increases in the synthesis (30–50%) and degradation (20–40%) of phosphatidylinositol 4‐monophosphate (DPI) and phosphatidylinositol 4,5‐bisphosphate (TPI) in a cell line which is mitogenically responsive to both growth factors. The increases in synthesis were time and dose dependent in a manner which was consistent with their involvement in mitogenesis; the increases were observed only under conditions where a mitogenic response occurred. While it has been suggested that an increased synthesis of phosphatidylinositol (PI) is coupled to the stimulation of DPI and TPI synthesis, we found that thrombin stimulated an early synthesis PI but EGF did not. To further evaluate the involvement of PI in thrombin‐stimulated cell division we determined the time and dose dependence of the stimulated PI synthesis and found that it also occurred in a manner which was consistent with its involvement in thrombin‐stimulated cell division. Furthermore, the stimulated PI synthesis was not observed with nonmitogenic proteases or in cell lines which were not responsive to thrombin. These results demonstrate that the metabolism of DPI and TPI appears closely related to the mitogenic response generated by EGF and thrombin. However, an early stimulation of PI synthesis is not coupled to this metabolism and is not necessary for mitogenic stimulation by EGF. Thus, a stimulation of PI synthesis is not a valid measure of alterations in inositol‐containing phospholipids and what has been termed the “PI response.”
AB - The effects of growth factors on inositol‐containing phospholipids were investigated to test the hypothesis that alterations in their metabolism are involved in mitogenic stimulation. Thrombin and EGF stimulated comparable increases in the synthesis (30–50%) and degradation (20–40%) of phosphatidylinositol 4‐monophosphate (DPI) and phosphatidylinositol 4,5‐bisphosphate (TPI) in a cell line which is mitogenically responsive to both growth factors. The increases in synthesis were time and dose dependent in a manner which was consistent with their involvement in mitogenesis; the increases were observed only under conditions where a mitogenic response occurred. While it has been suggested that an increased synthesis of phosphatidylinositol (PI) is coupled to the stimulation of DPI and TPI synthesis, we found that thrombin stimulated an early synthesis PI but EGF did not. To further evaluate the involvement of PI in thrombin‐stimulated cell division we determined the time and dose dependence of the stimulated PI synthesis and found that it also occurred in a manner which was consistent with its involvement in thrombin‐stimulated cell division. Furthermore, the stimulated PI synthesis was not observed with nonmitogenic proteases or in cell lines which were not responsive to thrombin. These results demonstrate that the metabolism of DPI and TPI appears closely related to the mitogenic response generated by EGF and thrombin. However, an early stimulation of PI synthesis is not coupled to this metabolism and is not necessary for mitogenic stimulation by EGF. Thus, a stimulation of PI synthesis is not a valid measure of alterations in inositol‐containing phospholipids and what has been termed the “PI response.”
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U2 - 10.1002/jcp.1041250330
DO - 10.1002/jcp.1041250330
M3 - Article
C2 - 2999166
AN - SCOPUS:0022370111
SN - 0021-9541
VL - 125
SP - 582
EP - 590
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
IS - 3
ER -