A CONFORMATION-SPECIFIC ANTIPEPTIDE ANTIBODY TO THE BETA-TYPE PLATELET-DERIVED GROWTH-FACTOR RECEPTOR ALSO RECOGNIZES THE ACTIVATED EPIDERMAL GROWTH-FACTOR RECEPTOR

Earlier we reported the generation of a conformation-specific antibody (Ab P2) to the beta-type platelet-derived growth factor receptor (Bis hayee, S., Majumdar, S., Scher, C.D., and Khan, S. (1988) Mol. Cell. B iol. 8, 3696-3702). Ab P2 is directed to a 16-amino acid peptide s-Lys -Lys-Tyr-Gln-Gln-Val-Asp-Glu-Glu-Phe-Leu-Arg) of the cytoplasmic domai n of the receptor, and it recognized the phosphorylated platelet-deriv ed growth factor receptor but not the unphosphorylated receptor. We no w report that Ab P2 also interacts with the epidermal growth factor re ceptor and that the recognition is specific for a conformation induced by phosphorylation of the receptor; however, Ab P2 is not directed to phosphotyrosine. Studies conducted with P2-derived peptides suggest t hat the conformation-specific antibody is directed to an acidic tripep tide, Asp-Glu-Glu, and this sequence is also present in the cytoplasmi c domain of the epidermal growth factor receptor. With respect to the C terminus amino acid or ATP-binding site, Asp-Glu-Glu is located in d ifferent regions in these receptors; nevertheless, this tripeptide alo ng with the surrounding amino acids is cryptic in the unphosphorylated receptor, and tyrosine phosphorylation uncovers this site. This sugge sts that the Asp-Glu-Glu sequence may be important in receptor functio ns.