Targeting dual-specificity phosphatases: manipulating MAP kinase signalling and immune responses

被引:417
作者
Jeffrey, Kate L. [1 ]
Camps, Montserrat
Rommel, Christian
Mackay, Charles R.
机构
[1] Garvan Inst Med Res, Immunol & Inflammat Res Program, Sydney, NSW 2010, Australia
[2] Merck Serono SA, Merck Serono Res Ctr, CH-1202 Geneva, Switzerland
关键词
D O I
10.1038/nrd2289
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Dual-specificity phosphatases (DUSPs) are a subset of protein tyrosine phosphatases, many of which dephosphorylate threonine and tyrosine residues on mitogen-activated protein kinases (MAPKs), and hence are also referred to as MAPK phosphatases (MKPs). The regulated expression and activity of DUSP family members in different cells and tissues controls MAPK intensity and duration to determine the type of physiological response. For immune cells, DUSPs regulate responses in both positive and negative ways, and DUSP-deficient mice have been used to identify individual DUSPs as key regulators of immune responses. From a drug discovery perspective, DUSP family members are promising drug targets for manipulating MAPK-dependent immune responses in a cell-type and disease-context-dependent manner, to either boost or subdue immune responses in cancers, infectious diseases or inflammatory disorders.
引用
收藏
页码:391 / 403
页数:13
相关论文
共 169 条
  • [91] Knockout of ERK1 MAP kinase enhances synaptic plasticity in the striatum and facilitates striatal-mediated learning and memory
    Mazzucchelli, C
    Vantaggiato, C
    Ciamei, A
    Fasano, S
    Pakhotin, P
    Krezel, W
    Welzl, H
    Wolfer, DP
    Pagès, G
    Valverde, O
    Marowsky, A
    Porrazzo, A
    Orban, PC
    Maldonado, R
    Ehrengruber, MU
    Cestari, V
    Lipp, HP
    Chapman, PF
    Pouysségur, J
    Brambilla, R
    [J]. NEURON, 2002, 34 (05) : 807 - 820
  • [92] Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo
    Meng, TC
    Fukada, T
    Tonks, NK
    [J]. MOLECULAR CELL, 2002, 9 (02) : 387 - 399
  • [93] Activation of p38 mitogen-activated protein kinase in vivo selectively induces apoptosis of CD8+ but not CD4+ T cells
    Merritt, C
    Enslen, H
    Diehl, N
    Conze, D
    Davis, RJ
    Rincón, M
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (03) : 936 - 946
  • [94] Mourey RJ, 1996, J BIOL CHEM, V271, P3795
  • [95] The dual specificity phosphatases M3/6 and MKP-3 are highly selective for inactivation of distinct mitogen-activated protein kinases
    Muda, M
    Theodosiou, A
    Rodrigues, N
    Boschert, U
    Camps, M
    Gillieron, C
    Davies, K
    Ashworth, A
    Arkinstall, S
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (44) : 27205 - 27208
  • [96] Muda M, 1996, J BIOL CHEM, V271, P4319
  • [97] Identification of the human YVH1 protein-tyrosine phosphatase orthologue reveals a novel zinc binding domain essential for in vivo function
    Muda, M
    Manning, ER
    Orth, K
    Dixon, JE
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (34) : 23991 - 23995
  • [98] Molecular cloning and functional characterization of a novel mitogen-activated protein kinase phosphatase, MKP-4
    Muda, M
    Boschert, U
    Smith, A
    Antonsson, B
    Gillieron, C
    Chabert, C
    Camps, M
    Martinou, I
    Ashworth, A
    Arkinstall, S
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (08) : 5141 - 5151
  • [99] Molecular interpretation of ERK signal duration by immediate early gene products
    Murphy, LO
    Smith, S
    Chen, RH
    Fingar, DC
    Blenis, J
    [J]. NATURE CELL BIOLOGY, 2002, 4 (08) : 556 - 564
  • [100] Substrate recognition domains within extracellular signal-regulated kinase mediate binding and catalytic activation of mitogen-activated protein kinase phosphatase-3
    Nichols, A
    Camps, M
    Gillieron, C
    Chabert, C
    Brunet, A
    Wilsbacher, J
    Cobb, M
    Pouyssegur, J
    Shaw, JP
    Arkinstall, S
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (32) : 24613 - 24621