A PREDICTIVE SCALE FOR EVALUATING CYCLIN-DEPENDENT KINASE SUBSTRATES - A COMPARISON OF P34(CDC2) AND P33(CDK2)

Protein phosphorylation by members of the Cdk (cyclin dependent kinase ) family of protein kinases is necessary for progression through the c ell cycle. However, the primary sequence determinants of Cdk substrate specificity have get to be examined quantitatively. We have used a pa nel of glutathione S-transferase peptide fusions to investigate the fi ne-structure specificity of p33(cdk2) and p34(cdc2). Our data indicate that the generally held consensus sequences for p34(cdc2) represent a significant oversimplification of its true specificity and that this specificity is conserved between species. p33(cdk2) and p34(cdc2) have similar but distinct substrate specificities that are affected modest ly by the associated cyclin subunit, We derive specific values of phos phorylation efficiencies by these enzymes that can be used to estimate the phosphorylation potential of proposed Cdk substrates.