Hydrogen peroxide induces complex formation of SHC-Grb2-SOS
with receptor tyrosine kinase and activates Ras and extracellular
signal-regulated protein kinases group of mitogen-activated
protein kinases.
Author: Rao GN
Source: Oncogene 1996 Aug 15; 13(4):713-9
Abstract:
Protein tyrosine phosphorylation events play determinant
roles in cellular processes such as proliferation and
differentiation. We have recently reported that hydrogen peroxide,
an active oxygen species and a cellular oxidant, stimulates growth
response events in vascular smooth muscle cells (VSMC).
To understand the mechanisms by which oxidant stress modulates
these growth response events, we have studied the effect
of hydrogen peroxide on protein tyrosine phosphorylation
events in VSMC. Our findings show that hydrogen peroxide
stimulates tyrosine phosphorylation of several proteins
including epidermal growth factor receptor (EGFR) in VSMC.
Hydrogen peroxide-induced tyrosine phosphorylation of EGFR
was found to be time dependent; with a threefold increase
at 5 min and a 20-fold increase at 30 min of treatment
as compared to control levels. Hydrogen peroxide treatment
of VSMC also resulted in a time-dependent increase in tyrosine
phosphorylation of SHC proteins. In addition, hydrogen
peroxide-induced tyrosine-phosphorylated EGFR formed a
complex with SHC-Grb2-SOS. These events were followed by
activation of Ras and extracellular signal-regulated protein
kinases (ERKs) group of mitogen-activated protein kinases
(MAPKs). Together these findings demonstrate for the first
time that hydrogen peroxide, a cellular oxidant, possess
the ability to activate EGFR-mediated signaling events
in VSMC. These EGFR-mediated signaling events may be important
in oxidant stress-induced cellular responses.
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