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We have previously reported that epidermal growth factor (EGF) activates phospholipase A2 (PLA2) independently of phospholipase C (PLC) in renal mesangial cells. In this study we use NIH 3T3 cell lines transfected with the normal EGF receptor (HER14 cells) or with EGF receptor defective in tyrosine kinase activity (K721A cells), to determine whether the intrinsic tyrosine kinase activity of the EGF receptor is required for the PLC-independent activation of PLA2. Intact cells were preincubated with EGF or other ligands, and then PLA2 activity was assayed in cell-free extracts with 1-stearoyl-2-[14C]arachidonyl phosphatidylcholine as the substrate. In HER14 cells, EGF increased PLA2 activity by 226 +/- 30%, and the tumour promoter phorbol myristate acetate (PMA) increased activity by 223 +/- 30%. The effect of EGF was not mediated through protein kinase C (PKC), whose activation by EGF requires tyrosine kinase activity, since raising intracellular Ca2+ alone with the Ca2+ ionophore A23187 did not mimic its effect, and the effect of EGF persisted in PKC-down-regulated cells. In K721A cells EGF was ineffective, whereas PMA was still active. Furthermore, in intact HER14 cells prelabelled with [14C]arachidonate, EGF-stimulated release of [14C]arachidonic acid was synergistic with A23187, but was unaccompanied by a rise in [14C]diacylglycerol. EGF had no effect on [14C]arachidonic acid release in intact K721A cells. We conclude that the tyrosine kinase activity of the EGF receptor is necessary for the PLC-independent stimulation of PLA2 by EGF.
H J Goldberg, and
M M Viegas, and
B L Margolis, and
J Schlessinger, and
K L Skorecki
February 1990,
Molecular and cellular biology,
H J Goldberg, and
M M Viegas, and
B L Margolis, and
J Schlessinger, and
K L Skorecki
January 2000,
Analytical biochemistry,
H J Goldberg, and
M M Viegas, and
B L Margolis, and
J Schlessinger, and
K L Skorecki
January 2002,
Biochemical and biophysical research communications,
H J Goldberg, and
M M Viegas, and
B L Margolis, and
J Schlessinger, and
K L Skorecki
June 1986,
The Journal of biological chemistry,
H J Goldberg, and
M M Viegas, and
B L Margolis, and
J Schlessinger, and
K L Skorecki
August 1993,
Biochemistry,
H J Goldberg, and
M M Viegas, and
B L Margolis, and
J Schlessinger, and
K L Skorecki
June 2004,
British journal of cancer,
H J Goldberg, and
M M Viegas, and
B L Margolis, and
J Schlessinger, and
K L Skorecki
August 2002,
Current opinion in pharmacology,
H J Goldberg, and
M M Viegas, and
B L Margolis, and
J Schlessinger, and
K L Skorecki
December 2007,
Proceedings of the National Academy of Sciences of the United States of America,
H J Goldberg, and
M M Viegas, and
B L Margolis, and
J Schlessinger, and
K L Skorecki
August 2016,
Cancer science,
H J Goldberg, and
M M Viegas, and
B L Margolis, and
J Schlessinger, and
K L Skorecki
April 2003,
Experimental & molecular medicine,
