3-PHOSPHOHISTIDINE CANNOT REPLACE PHOSPHOTYROSINE IN HIGH-AFFINITY BINDING TO PHOSPHOTYROSINE BINDING OR SRC HOMOLOGY-2 DOMAINS

Posttranslational phosphorylation of proteins is an important event in many cellular processes, Phosphorylated tyrosine residues can serve a s association sites for other proteins in signal transduction cascades of tyrosine kinase receptors. Formation of phosphohistidine residues in proteins has been found in eukaryotic and prokaryotic organisms. Fu rthermore, it has been suggested that phosphohistidine might substitut e for phosphotyrosine in conferring high-affinity binding to proteins involved in signal transduction, We have analyzed the ability of 3-pho sphohistidine to associate with the known phosphotyrosine-specific pho sphotyrosine binding and src homology 2 protein domains. From our bind ing studies using synthetic peptides, we conclude that 3-phosphohistid ine cannot replace phosphotyrosine in conferring high-affinity binding to the phosphotyrosine binding domain of she or the src homology 2 do main of phospholipase C-gamma 1.