Home LiteratureArticle Details

PMID: 8887677 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A 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.

Molecular and cellular biology ·Vol. 16 ·No. 11 ·1996-11-00 ·Pages 6486-93

Songyang Z, Lu KP, Kwon YT, Tsai LH, Filhol O, Cochet C, Brickey DA, Soderling TR, Bartleson C, Graves DJ, DeMaggio AJ, Hoekstra MF, Blenis J, Hunter T, Cantley LC

Abstract

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.

MeSH Terms

Amino Acid Sequence CDC2-CDC28 Kinases Caenorhabditis elegans Proteins Calcium-Calmodulin-Dependent Protein Kinase Type 2 Calcium-Calmodulin-Dependent Protein Kinases/chemistry,metabolism Calmodulin-Binding Proteins/chemistry,metabolism Casein Kinase II Casein Kinases Cell Cycle Proteins Crystallography, X-Ray Cyclic AMP-Dependent Protein Kinases/chemistry,metabolism Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinase 5 Cyclin-Dependent Kinases/chemistry,metabolism Databases, Factual Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases Models, Molecular Muscle Proteins/chemistry,metabolism NIMA-Related Kinase 1 NIMA-Related Kinases Oligopeptides/chemistry,metabolism Phosphopeptides/chemistry,isolation & purification Phosphorylase Kinase/metabolism Protein Conformation Protein Kinases/chemistry,metabolism Protein Serine-Threonine Kinases/chemistry,metabolism Substrate Specificity

Chemicals

Caenorhabditis elegans Proteins Calmodulin-Binding Proteins Cell Cycle Proteins Muscle Proteins Oligopeptides Phosphopeptides unc-22 protein, C elegans Protein Kinases Phosphorylase Kinase Casein Kinase II Casein Kinases Cyclin-Dependent Kinase 5 NIMA-Related Kinase 1 NIMA-Related Kinases NIMA-related kinase 6 Protein Serine-Threonine Kinases Cyclic AMP-Dependent Protein Kinases Calcium-Calmodulin-Dependent Protein Kinase Type 2 Calcium-Calmodulin-Dependent Protein Kinases unc-43 protein, C elegans CDC2-CDC28 Kinases Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinases Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases

Authors & Affiliations

15 authors, click to expand affiliations / ORCID

Songyang Z

Division of Signal Transduction, Beth Israel Hospital, Boston, Massachusetts 02215, USA.

Lu K P

Kwon Y T

Tsai L H

Filhol O

Cochet C

Brickey D A

Soderling T R

Bartleson C

Graves D J

DeMaggio A J

Hoekstra M F

Blenis J

Hunter T

Cantley L C

References (25)

25 references, click to expand

Phosphorylation of the TAL1 oncoprotein by the extracellular-signal-regulated protein kinase ERK1.
Mol Cell Biol. 1993 Feb;13(2):801-8 PMID: 8423803
Crystal structure of the tyrosine kinase domain of the human insulin receptor.
Nature. 1994 Dec 22-29;372(6508):746-54 PMID: 7997262
The protein kinase family: conserved features and deduced phylogeny of the catalytic domains.
Science. 1988 Jul 1;241(4861):42-52 PMID: 3291115
Phosphate groups as substrate determinants for casein kinase I action.
J Biol Chem. 1990 Aug 25;265(24):14264-9 PMID: 2117608
Structure of a peptide inhibitor bound to the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase.
Science. 1991 Jul 26;253(5018):414-20 PMID: 1862343
Parallel activation of the NIMA and p34cdc2 cell cycle-regulated protein kinases is required to initiate mitosis in A. nidulans.
Cell. 1991 Oct 18;67(2):283-91 PMID: 1913824
Identification of substrate recognition determinants for human ERK1 and ERK2 protein kinases.
J Biol Chem. 1991 Nov 25;266(33):22159-63 PMID: 1939237
Protein kinase catalytic domain sequence database: identification of conserved features of primary structure and classification of family members.
Methods Enzymol. 1991;200:38-62 PMID: 1956325
Protein kinase phosphorylation site sequences and consensus specificity motifs: tabulations.
Methods Enzymol. 1991;200:62-81 PMID: 1956339
ERK1 and ERK2, two microtubule-associated protein 2 kinases, mediate the phosphorylation of tyrosine hydroxylase at serine-31 in situ.
Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2365-9 PMID: 1347949
Identification of mitogen-activated protein kinase phosphorylation sequences in mammalian h-Caldesmon.
FEBS Lett. 1993 May 3;322(1):56-60 PMID: 8482368
Crystal structure of cyclin-dependent kinase 2.
Nature. 1993 Jun 17;363(6430):595-602 PMID: 8510751
cdc2-like kinase from rat spinal cord specifically phosphorylates KSPXK motifs in neurofilament proteins: isolation and characterization.
Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6844-8 PMID: 8341707
CAK, the p34cdc2 activating kinase, contains a protein identical or closely related to p40MO15.
EMBO J. 1993 Aug;12(8):3133-42 PMID: 8344252
Phosphorylase kinase, a metal ion-dependent dual specificity kinase.
J Biol Chem. 1993 Aug 25;268(24):17683-6 PMID: 8349652
Identification of a human epidermal growth factor receptor-associated protein kinase as a new member of the mitogen-activated protein kinase/extracellular signal-regulated protein kinase family.
J Biol Chem. 1993 Aug 25;268(24):18213-7 PMID: 7688742
Determination of v-Mos-catalyzed phosphorylation sites and autophosphorylation sites on MAP kinase kinase by ESI/MS.
Biochemistry. 1995 Feb 28;34(8):2610-20 PMID: 7873542
Use of an oriented peptide library to determine the optimal substrates of protein kinases.
Curr Biol. 1994 Nov 1;4(11):973-82 PMID: 7874496
Crystal structure of casein kinase-1, a phosphate-directed protein kinase.
EMBO J. 1995 Mar 1;14(5):1015-23 PMID: 7889932
Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex.
Nature. 1995 Jul 27;376(6538):313-20 PMID: 7630397
Atomic structure of the MAP kinase ERK2 at 2.3 A resolution.
Nature. 1994 Feb 24;367(6465):704-11 PMID: 8107865
Identification of substrate specificity determinants for the cell cycle-regulated NIMA protein kinase.
J Biol Chem. 1994 Mar 4;269(9):6603-7 PMID: 8120013
Cell-cycle-regulated phosphorylation of oncoprotein 18 on Ser16, Ser25 and Ser38.
Eur J Biochem. 1994 Mar 1;220(2):359-68 PMID: 8125092
Insights into autoregulation from the crystal structure of twitchin kinase.
Nature. 1994 Jun 16;369(6481):581-4 PMID: 8202162
Substrate specificity determinants for casein kinase II as deduced from studies with synthetic peptides.
J Biol Chem. 1987 Jul 5;262(19):9136-40 PMID: 3474230

Article Info

Journal

Molecular and cellular biology

Abbr.

Mol Cell Biol

ISSN

0270-7306

DOI

10.1128/MCB.16.11.6486

Published

1996-11-00

Pages

6486-93

Language

English

Region

United States

NLM ID

8109087

PMCID

PMC231650

Subset

Grants

NIGMS NIH HHS · R01 GM056203 · United States

External Links

PubMed source DOI: 10.1128/MCB.16.11.6486 PMC Full Text View journal details

Analysis Services

A 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.

Contact

WeChat Official Account