Adjacent carboxyterminal tyrosine phosphorylation events identify functionally distinct ErbB2 receptor subsets: implications for molecular diagnostics

Experimental Cell Research
X OuyangR J Epstein

Abstract

Site-directed mutagenesis can define the effects of altering one or more amino acids within a protein, but this technique may lack sensitivity when used to characterize proteins which differ conformationally or posttranslationally at multiple sites. A novel alternative approach involves the direct characterization of wild-type protein isoforms identified by site-specific immunodetection. To this end we have developed antibodies which recognize ErbB2 subsets characterized by adjacent tyrosine phosphorylation events (Y1222 and Y1248) in the C-terminal tail of the oncoprotein. Here we use these phosphoantibodies to demonstrate the existence of tyrosine-phosphorylated ErbB2 subsets which differ in their patterns of heterooligomer formation, in vitro autophosphorylation, and recruitment of SH2-containing substrates. Furthermore, Y1222 and/or Y1248 phosphoantibody immunoreactivity is readily detectable in ErbB2-overexpressing human breast tumors, in which context these phosphorylation events exhibit significant discordance. These data confirm the value of site-specific immunodetection as a strategy for characterizing phosphoprotein function in vitro and in vivo and suggest that multisite phosphotyping of human tumors may contribute n...Continue Reading

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Citations

May 4, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yoon Pin Lim

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