A conformation-specific anti-peptide 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 (Bishayee, S., Majumdar, S., Scher, C. D., and Khan, S. (1988) Mol. Cell. Biol. 8, 3696-3702). Ab P2 is directed to a 16-amino acid peptide (Glu-Gly-Tyr-Lys-Lys-Lys-Tyr-Gln-Gln-Val-Asp-Glu-Glu-Phe-Leu-Arg) of the cytoplasmic domain of the receptor, and it recognizes the phosphorylated platelet-derived growth factor receptor but not the unphosphorylated receptor. We now report that Ab P2 also interacts with the epidermal growth factor receptor 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 that the conformation-specific antibody is directed to an acidic tripeptide, Asp-Glu-Glu, and this sequence is also present in the cytoplasmic 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 different regions in these receptors; nevertheless, this tripeptide along with the surrounding amino acids is cryptic in the unphosphorylated receptor, and tyrosine phosphorylation uncovers this site. This suggests that the Asp-Glu-Glu sequence may be important in receptor functions.
Panneerselvam
K
K
Coriell Institute for Medical Research, Camden, New Jersey 08103, USA.
Reitz
H
H
Khan
S A
SA
Bishayee
S
S
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001666:Binding Sites, Antibody; D002460:Cell Line; D003429:Cross Reactions; D066246:ErbB Receptors / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D010766:Phosphorylation; D011487:Protein Conformation; D017479:Receptors, Platelet-Derived Growth Factor / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000906:Antibodies; D010455:Peptides; D066246:ErbB Receptors; D017479:Receptors, Platelet-Derived Growth Factor