THE INTRACELLULAR TYROSINE KINASE DOMAIN OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR UNDERGOES A CONFORMATIONAL CHANGE UPON AUTOPHOSPHORYLATION

The intracellular portion of the epidermal growth factor receptor cons ists of a tyrosine kinase domain of approximately 290 amino acids and a COOH-terminal regulatory domain of approximately 230 amino acids tha t contains five sites of autophosphorylation. The effect of autophosph orylation on the conformation of the intracellular domain has been ana lyzed using gel filtration. Both phosphorylated and dephosphorylated f orms of the intracellular domain exist as monomers and as dimers and a ppear to have an extended conformation. The Stokes' radii of phosphory lated monomers and dimers were larger than those of the dephosphorylat ed forms, indicating that the dephosphorylated form is more compact. T hese results indicate that a significant conformational change occurs in the intracellular portion of the epidermal growth factor receptor u pon tyrosine autophosphorylation.