Activation of the Jnk signaling pathway by a dual-specificity phosphatase, JS']JSP-1

被引:73
作者
Shen, Y
Luche, R
Wei, B
Gordon, ML
Diltz, CD
Tonks, NK
机构
[1] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA
[2] CEPTYR Inc, Bothell, WA 98021 USA
关键词
D O I
10.1073/pnas.231499098
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The mitogen-activated protein kinases (MAPKs) are integral to the mechanisms by which cells respond to physiological stimuli, such as growth factors, hormones, and cytokines, and to a wide variety of environmental stresses. The MAPKs, which are stimulated by phosphorylation of a TXY motif in their activation loop, are components of signal transduction cascades in which sequential activation of protein kinases culminates in their activation and their subsequent phosphorylation of various effector proteins that mediate the physiological response. MAPKs are also subject to dephosphorylation and inactivation, both by enzymes that recognize the residues of the TXY motif independently and by dual specificity phosphatases, which dephosphroylate both Tyr and Ser/Thr residues. We report the identification and characterization of a novel dual specificity phosphatase. Contrary to expectation, this broadly expressed enzyme did not inactivate MAPKs in transient cotransfection assays but instead displayed the capacity to function as a selective activator of the MAPK ink, hence the name, Jnk Stimulatory Phosphatase-1 (JSP-1). This study illustrates a new aspect of the regulation of MAPK-dependent signal transduction and raises the possibility that JSP-1 may offer a different perspective to the study of various inflammatory and proliferative disorders associated with dysfunctional ink signaling.
引用
收藏
页码:13613 / 13618
页数:6
相关论文
共 27 条
[1]   CRYSTAL-STRUCTURE OF HUMAN PROTEIN-TYROSINE-PHOSPHATASE 1B [J].
BARFORD, D ;
FLINT, AJ ;
TONKS, NK .
SCIENCE, 1994, 263 (5152) :1397-1404
[2]   Dual specificity phosphatases: a gene family for control of MAP kinase function [J].
Camps, M ;
Nichols, A ;
Arkinstall, S .
FASEB JOURNAL, 2000, 14 (01) :6-16
[3]  
CHNG L, 2001, NATURE, V410, P37
[4]   Signal transduction by the JNK group of MAP kinases [J].
Davis, RJ .
CELL, 2000, 103 (02) :239-252
[5]   THE PURIFICATION AND CHARACTERIZATION OF A HUMAN DUAL-SPECIFIC PROTEIN-TYROSINE-PHOSPHATASE [J].
DENU, JM ;
ZHOU, GC ;
WU, L ;
ZHAO, R ;
YUVANIYAMA, JD ;
SAPER, MA ;
DIXON, JE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (08) :3796-3803
[6]   MEKKs, GCKs, MLKs, PAKs, TAKs, and Tpls: Upstream regulators of the c-Jun amino-terminal kinases? [J].
Fanger, GR ;
Gerwins, P ;
Widmann, C ;
Jarpe, MB ;
Johnson, GL .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 1997, 7 (01) :67-74
[7]   MKK7 is a stress-activated mitogen-activated protein kinase kinase functionally related to hemipterous [J].
Holland, PM ;
Suzanne, M ;
Campbell, JS ;
Noselli, S ;
Cooper, JA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (40) :24994-24998
[8]   Protein phosphatases and the regulation of mitogen-activated protein kinase signalling [J].
Keyse, SM .
CURRENT OPINION IN CELL BIOLOGY, 2000, 12 (02) :186-192
[9]   Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation [J].
Kyriakis, JM ;
Avruch, J .
PHYSIOLOGICAL REVIEWS, 2001, 81 (02) :807-869
[10]   Synergistic activation of SAPK1/JNK1 by two MAP kinase kinases in vitro [J].
Lawler, S ;
Fleming, Y ;
Goedert, M ;
Cohen, P .
CURRENT BIOLOGY, 1998, 8 (25) :1387-1390