IN-VITRO SUBSTRATE-SPECIFICITY OF PROTEIN-TYROSINE KINASES

Synthetic peptides such as P60(src) autophosphorylation site peptides and angiotensin are indiscriminately phosphorylated by protein tyrosin e kinases. The observation has led to the general belief that protein tyrosine kinases are highly promiscuous, displaying little in vitro si te specificity. In recent years, evidence has been accumulating to ind icate that such a belief requires close examination. Synthetic peptide s showing high substrate activity for specific groups of protein tyros ine kinases have been obtained. Systematic modification of certain sub strate peptides suggests that kinase substrate determinants reside wit h specific amino acid residues proximal to the target tyrosine. A numb er of protein kinases have been shown to be regulated by tyrosine phos phorylation at specific sites by highly specific protein tyrosine kina ses. These and other selected biochemical studies that contribute to t he evolving view of in vitro substrate specificity of protein tyrosine kinases are reviewed.