Open AccessA Structural Basis for Substrate Specificities of Protein Ser/Thr Kinases: Primary Sequence Preference of Casein Kinases I and II, NIMA, Phosphorylase Kinase, Calmodulin-Dependent Kinase II, CDK5, and Erk1
Author(s) -
Zhou Songyang,
Kun Ping Lu,
Young T. Kwon,
Li Huei Tsai,
Odile Filhol,
Claude Cochet,
Debra A. Brickey,
Thomas R. Soderling,
Cheryl Bartleson,
Donald J. Graves,
Anthony J. Demaggio,
Merl F. Hoekstra,
John Blenis,
Tony Hunter,
Lewis C. Cantley
Publication year - 1996
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.16.11.6486
Subject(s) - kinase , biology , biochemistry , casein kinase 1 , map2k7 , sh3 domain , cyclin dependent kinase 2 , protein serine threonine kinases , mapk14 , phosphorylase kinase , c raf , mitogen activated protein kinase kinase , glycogen phosphorylase , casein kinase 2 , protein kinase a , enzyme , proto oncogene tyrosine protein kinase src
We have developed a method to study the primary sequence specificities of protein kinases by using an oriented degenerate peptide library. We report here the substrate specificities of eight protein Ser/Thr kinases. All of the kinases studied selected distinct optimal substrates. The identified substrate specificities of these kinases, together with known crystal structures of protein kinase A, CDK2, Erk2, twitchin, and casein kinase I, provide a structural basis for the substrate recognition of protein Ser/Thr kinases. In particular, the specific selection of amino acids at the +1 and -3 positions to the substrate serine/threonine can be rationalized on the basis of sequences of protein kinases. The identification of optimal peptide substrates of CDK5, casein kinases I and II, NIMA, calmodulin-dependent kinases, Erk1, and phosphorylase kinase makes it possible to predict the potential in vivo targets of these kinases.