Protein kinase specificity. A strategic collaboration between kinase peptide specificity and substrate recruitment

Specificity of phosphorylation by protein kinases is essential to the integrity of biological signal transduction. Specificity is determined by two critical elements: (1) peptide specificity of the kinase, i. e., preferential phosphorylation of S/T/Y residues surrounded by particular patterns of amino acids; and (2) recruitment, i. e., increasing the frequency of encounter between kinase and substrate. Historically, the importance of peptide specificity was studied first, but it has been somewhat overshadowed by emerging emphasis on the importance of recruitment. Recent studies confirm and extend understanding of the relative contribution of these two elements. Peptide specificity always constrains the range of sites that can be phosphorylated by a kinase. Only when recruitment is very strong, as in the case with autophosphorylation, can markedly suboptimal substrates be phosphorylated.