TY - JOUR
T1 - Evidence for protein kinase C independent activation of phospholipase D by phorbol esters in lymphocytes
AU - Cao, Yu Zhang
AU - Reddy, C. Channa
AU - Mastro, Andrea M.
N1 - Funding Information:
This work was supported by an Intercollegiate Research Project grant from the College of Agriculture, Penn State University to Drs. A. M. Mastro, C. C. Reddy and R. W. Scholz and by grants from the National Institutes of Health, NCI, CA24385 (to A. M. Mastro) and HL31245, CA37979 (to C. C. Reddy).
PY - 1990/9/28
Y1 - 1990/9/28
N2 - Recently it was reported that tumor-promoting phorbol esters stimulate the production of phosphatidylethanol (PEt) in lymphocytes through the activation of phospholipase D (PLD). However, it remains unclear whether this activation is mediated through protein kinase (PKC). The study reported here shows that tumor promoters 12-0-tetradecanoylphorbol-13-acetate (TPA), phorbol dibutyrate (PDBU), 12-deoxyphorbol-13-phenylacetate (DOPP), 12-deoxyphorbol-13-phenylacetate-20-acetate (DOPPA) and mezerin activated PLD, as measured by the formation of PEt, whereas Concanavalin A (ConA) had no effect. Inhibitors of PKC, spingosine (2×10-6M - 5×10-6M), H-7, HA1004 (5×10-7 - 5×10-6M) and K252a (1×10-7 - 1×10-6M) failed to block the PEt synthesis induced by TPA. In fact, sphingosine increased it. Other PKC activators, 1-oleoyl-2-acetylglycerol (OAG) and dioctanoylglycerol (DiC8) had no effect on lymphocyte PLD activity. Analysis of the phospholipid contents after stimulation by TPA showed that only phosphatidylcholine (PC) was significantly decreased. Interestingly, TPA activated PLD in intact cells but not in lysates or subcellular fractions. These observations suggest that stimulation of PLD-catalyzed PEt synthesis by TPA is not solely mediated through PKC activation.
AB - Recently it was reported that tumor-promoting phorbol esters stimulate the production of phosphatidylethanol (PEt) in lymphocytes through the activation of phospholipase D (PLD). However, it remains unclear whether this activation is mediated through protein kinase (PKC). The study reported here shows that tumor promoters 12-0-tetradecanoylphorbol-13-acetate (TPA), phorbol dibutyrate (PDBU), 12-deoxyphorbol-13-phenylacetate (DOPP), 12-deoxyphorbol-13-phenylacetate-20-acetate (DOPPA) and mezerin activated PLD, as measured by the formation of PEt, whereas Concanavalin A (ConA) had no effect. Inhibitors of PKC, spingosine (2×10-6M - 5×10-6M), H-7, HA1004 (5×10-7 - 5×10-6M) and K252a (1×10-7 - 1×10-6M) failed to block the PEt synthesis induced by TPA. In fact, sphingosine increased it. Other PKC activators, 1-oleoyl-2-acetylglycerol (OAG) and dioctanoylglycerol (DiC8) had no effect on lymphocyte PLD activity. Analysis of the phospholipid contents after stimulation by TPA showed that only phosphatidylcholine (PC) was significantly decreased. Interestingly, TPA activated PLD in intact cells but not in lysates or subcellular fractions. These observations suggest that stimulation of PLD-catalyzed PEt synthesis by TPA is not solely mediated through PKC activation.
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U2 - 10.1016/0006-291X(90)90777-K
DO - 10.1016/0006-291X(90)90777-K
M3 - Article
C2 - 2222456
AN - SCOPUS:0025078251
SN - 0006-291X
VL - 171
SP - 955
EP - 962
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -