Differential tyrosine phosphorylation of phospholipase D isozymes by hydrogen peroxide and the epidermal growth factor in A431 epidermoid carcinoma cells
Ds. Min et al., Differential tyrosine phosphorylation of phospholipase D isozymes by hydrogen peroxide and the epidermal growth factor in A431 epidermoid carcinoma cells, MOL CELLS, 11(3), 2001, pp. 369-378
The regulatory mechanism through which the phospholipase D (PLD) isoforms P
LD1 and PLD2 are activated is poorly understood, We investigated the possib
ility that the PLD isozymes are differentially regulated in response to pha
rmacologic stimulants in cells, In this report, we demonstrate for the firs
t time that H2O2 and EGF differentially induce tyrosine phosphorylation of
the PLD isozymes in A431 cells, which express both PLD1 and PLD2, H2O2 indu
ced tyrosine phosphorylation of PLD1 and PLD2, whereas EGF only caused the
tyrosine phosphorylation of PLD2, Both agents also induced phosphorylation
of the EGF receptor, Interestingly, the PLD isozymes were associated with t
he EGF receptor and PKC-alpha in a ligand independent manner, Activation of
PLD by H2O2 and EGF nearly correlated with tyrosine phosphorylation of the
protein in PLD1 immune complexes. Activation of PLD by both agents was inh
ibited by the PKC inhibitor, Ro 31-8220, and by the down-regulation of PI(C
, Pretreatment of the cells with the tyrosine kinase inhibitor tyrphostin A
G1478 resulted in inhibition of the H2O2 and EGF-induced tyrosine phosphory
lation and PLD activation, These results indicate that H2O2 and EGF induce
differential tyrosine phosphorylation of PLD isozymes, Also, the activation
of PLD by these agonists involves tyrosine phosphorylation and PKC activat
ion.