Journal of Biochemistry Advance Access originally published online on October 23, 2007
Journal of Biochemistry 2008 143(1):31-38; doi:10.1093/jb/mvm190
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© 2007 The Japanese Biochemical Society.
Epidermal Growth Factor Receptor Phosphorylates Protein Kinase C 
at Tyr332 to form a Trimeric Complex with p66Shc in the H2O2-stimulated Cells
1Biosignal Research Center; and 2Research Center for Environmental Genomics, Kobe University, Kobe 657-8501, Japan
*To whom correspondence should be addressed. Tel: + 81-78-803-5964, Fax: +81-78-803-5972, E-mail: ukikkawa{at}kobe-u.ac.jp
Received August 31, 2007; Accepted September 30, 2007
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Abstract |
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Protein kinase C (PKC) 
is phosphorylated at Tyr311 and Tyr332 and its catalytic activity is enhanced in the H2O2-stimulated cells, but the enzymes that recognize these tyrosine residues, especially Tyr332, have been remained to be clarified. The analysis of the endogenous proteins in COS-7 cells revealed that PKC binds to p66Shc, an adaptor protein containing two phosphotyrosine-binding domains, in a manner dependent on its tyrosine phosphorylation upon H2O2 stimulation. The studies using the mutated PKC clarified that PKC associates with p66Shc through the phosphorylated Tyr332 residue. Epidermal growth factor (EGF) receptor was detected in the anti-p66Shc immunoprecipitate prepared from the H2O2-stimulated cells, and this receptor-type tyrosine kinase phosphorylated PKC at Tyr332 in vitro. PKC was, however, not tyrosine phosphorylated in the EGF-stimulated cells, whereas H2O2-induced tyrosine phosphorylation of PKC and its association with p66Shc were strongly suppressed by EGF receptor kinase inhibitors such as AG1478 and PD153035. These results indicate that EGF receptor phosphorylates PKC at Tyr332 in the H2O2-stimulated but not in the growth-factor treated cells, and suggest that PKC in the complex with p66Shc and EGF receptor may play a role in the stress-signalling pathway.
Key Words:
complex formation, EGF receptor, hydrogen peroxide, PKC, Shc
Abbreviations: CH, collagen-homology; EGF, epidermal growth factor; EGFR, EGF receptor; GFP, green fluorescent protein; GST, glutathione S-transferase; PKC, protein kinase C; PTB, phosphotyrosine-binding; SH2, Src homology 2
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