OxyFile #227

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.