Activation mechanism of the MAP kinase ERK2 by dual phosphorylation

被引:620
作者
Canagarajah, BJ
Khokhlatchev, A
Cobb, MH
Goldsmith, EJ
机构
[1] UNIV TEXAS, SW MED CTR, DEPT BIOCHEM, DALLAS, TX 75235 USA
[2] UNIV TEXAS, SW MED CTR, DEPT PHARMACOL, DALLAS, TX 75235 USA
关键词
D O I
10.1016/S0092-8674(00)80351-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The structure of the active form of the MAP kinase ERK2 has been solved, phosphorylated on a threonine and a tyrosine residue within the phosphorylation lip. The lip is refolded, bringing the phosphothreonine and phosphotyrosine into alignment with surface arginine-rich binding sites. Conformational changes occur in the lip and neighboring structures, including the P+1 site, the MAP kinase insertion, the C-terminal extension, and helix C. Domain rotation and remodeling of the proline-directed P+1 specificity pocket account for the activation. The conformation of the P+1 pocket is similar to a second proline-directed kinase, CDK2-CyclinA, thus permitting the origin of this specificity to be defined. Conformational changes outside the lip provide loci at which the state of phosphorylation can be felt by other cellular components.
引用
收藏
页码:859 / 869
页数:11
相关论文
共 75 条
[1]  
AHN NG, 1991, J BIOL CHEM, V266, P4220
[2]   REQUIREMENT FOR INTEGRATION OF SIGNALS FROM 2 DISTINCT PHOSPHORYLATION PATHWAYS FOR ACTIVATION OF MAP KINASE [J].
ANDERSON, NG ;
MALLER, JL ;
TONKS, NK ;
STURGILL, TW .
NATURE, 1990, 343 (6259) :651-653
[3]   A FAST ALGORITHM FOR RENDERING SPACE-FILLING MOLECULE PICTURES [J].
BACON, D ;
ANDERSON, WF .
JOURNAL OF MOLECULAR GRAPHICS, 1988, 6 (04) :219-220
[4]   THE CCP4 SUITE - PROGRAMS FOR PROTEIN CRYSTALLOGRAPHY [J].
BAILEY, S .
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1994, 50 :760-763
[5]   IDENTIFICATION OF MULTIPLE EXTRACELLULAR SIGNAL-REGULATED KINASES (ERKS) WITH ANTIPEPTIDE ANTIBODIES [J].
BOULTON, TG ;
COBB, MH .
CELL REGULATION, 1991, 2 (05) :357-371
[6]   AN INSULIN-STIMULATED PROTEIN-KINASE SIMILAR TO YEAST KINASES INVOLVED IN CELL-CYCLE CONTROL [J].
BOULTON, TG ;
YANCOPOULOS, GD ;
GREGORY, JS ;
SLAUGHTER, C ;
MOOMAW, C ;
HSU, J ;
COBB, MH .
SCIENCE, 1990, 249 (4964) :64-67
[7]   ERKS - A FAMILY OF PROTEIN-SERINE THREONINE KINASES THAT ARE ACTIVATED AND TYROSINE PHOSPHORYLATED IN RESPONSE TO INSULIN AND NGF [J].
BOULTON, TG ;
NYE, SH ;
ROBBINS, DJ ;
IP, NY ;
RADZIEJEWSKA, E ;
MORGENBESSER, SD ;
DEPINHO, RA ;
PANAYOTATOS, N ;
COBB, MH ;
YANCOPOULOS, GD .
CELL, 1991, 65 (04) :663-675
[8]   Crystal structure and mutational analysis the human CDK2 kinase complex with cell cycle-regulatory protein CksHs1 [J].
Bourne, Y ;
Watson, MH ;
Hickey, MJ ;
Holmes, W ;
Rocque, W ;
Reed, SI ;
Tainer, JA .
CELL, 1996, 84 (06) :863-874
[9]   Identification of MAP kinase domains by redirecting stress signals into growth factor responses [J].
Brunet, A ;
Pouyssegur, J .
SCIENCE, 1996, 272 (5268) :1652-1655
[10]  
BRUNGER AT, 1992, XPLOR VERSION 3 1 SY