p38MAPK: stress responses from molecular mechanisms to therapeutics

被引：524

作者：

Coulthard, Lydia R. ^{[2
]}

White, Danielle E. ^{[1
]}

Jones, Dominic L. ^{[2
]}

McDermott, Michael F. ^{[2
]}

Burchill, Susan A. ^{[1
]}

机构：

[1] St James Univ Hosp, Candlelighters Childrens Canc Res Grp, LIMM, Leeds LS9 7TF, W Yorkshire, England

[2] St James Univ Hosp, NIHR Leeds Musculoskeletal Biomed Res Unit, Leeds LS9 7TF, W Yorkshire, England

来源：

TRENDS IN MOLECULAR MEDICINE | 2009年 / 15卷 / 08期

关键词：

ACTIVATED PROTEIN-KINASE; P38 MAP KINASE; NF-KAPPA-B; SPINAL MICROGLIA CONTRIBUTES; BRONCHIAL EPITHELIAL-CELLS; SIGNAL-REGULATED KINASE; TERMINAL KINASE; DIFFERENTIAL REGULATION; IL-6; PRODUCTION; NERVE LIGATION;

D O I：

10.1016/j.molmed.2009.06.005

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 p38(MAPK) protein kinases affect a variety of intracellular responses, with well-recognized roles in inflammation, cell-cycle regulation, cell death, development, differentiation, senescence and tumorigenesis. In this review, we examine the regulatory and effector components of this pathway, focusing on their emerging roles in biological processes involved in different pathologies. We summarize how this pathway has been exploited for the development of therapeutics and discuss the potential obstacles of targeting this promiscuous protein kinase pathway for the treatment of different diseases. Furthermore, we discuss how the p38(MAPK) pathway might be best exploited for the development of more effective therapeutics with minimal side effects in a range of specific disease settings.

引用

收藏

页码：369 / 379

页数：11

相关论文

共 128 条

[1] Cell cycle regulation by p38 MAP kinases [J].

Ambrosino, C ;

Nebreda, AR .

BIOLOGY OF THE CELL, 2001, 93 (1-2) :47-51

[2] Interleukin-18 induces angiogenic factors in rheumatoid arthritis synovial tissue fibroblasts via distinct signaling pathways [J].

Amin, Mohammad A. ;

Mansfield, Pamela J. ;

Pakozdi, Angela ;

Campbell, Phillip L. ;

Ahmed, Salahuddin ;

Martinez, Rita J. ;

Koch, Alisa E. .

ARTHRITIS AND RHEUMATISM, 2007, 56 (06) :1787-1797

[3] The kinases MSK1 and MSK2 act as negative regulators of Toll-like receptor signaling [J].

Ananieva, Olga ;

Darragh, Joanne ;

Johansen, Claus ;

Carr, Julia M. ;

McIlrath, Joanne ;

Park, Jin Mo ;

Wingate, Andrew ;

Monk, Claire E. ;

Toth, Rachel ;

Santos, Susana G. ;

Iversen, Lars ;

Arthur, J. Simon C. .

NATURE IMMUNOLOGY, 2008, 9 (09) :1028-1036

[4] Biphenyl amide p38 kinase inhibitors 4: DFG-in and DFG-out binding modes [J].

Angell, Richard M. ;

Angell, Tony D. ;

Bamborough, Paul ;

Bamford, Mark J. ;

Chung, Chun-wa ;

Cockerill, Stuart G. ;

Flack, Stephen S. ;

Jones, Katherine L. ;

Laine, Dramane I. ;

Longstaff, Timothy ;

Ludbrook, Steve ;

Pearson, Rosannah ;

Smith, Kathryn J. ;

Smee, Penny A. ;

Somers, Don O. ;

Walker, Ann L. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (15) :4433-4437

[5] Role of MAPKs in development and differentiation: lessons from knockout mice [J].

Aouadi, M. ;

Binetruy, B. ;

Caron, L. ;

Le Marchand-Brustel, Y. ;

Bost, F. .

BIOCHIMIE, 2006, 88 (09) :1091-1098

[6] The selectivity of protein kinase inhibitors: a further update [J].

Bain, Jenny ;

Plater, Lorna ;

Elliott, Matt ;

Shpiro, Natalia ;

Hastie, C. James ;

Mclauchlan, Hilary ;

Klevernic, Iva ;

Arthur, J. Simon C. ;

Alessi, Dario R. ;

Cohen, Philip .

BIOCHEMICAL JOURNAL, 2007, 408 :297-315

[7] Critical role of nuclear factor-κB and stress-activated protein kinases in steroid unresponsiveness [J].

Bantel, H ;

Schmitz, ML ;

Raible, A ;

Gregor, M ;

Schulze-Osthoff, K .

FASEB JOURNAL, 2002, 16 (13) :1832-+

[8] Targeting p38-MAPK in the ischaemic heart: kill or cure? [J].

Bassi, Rekha ;

Heads, Richard ;

Marber, Michael S. ;

Clark, James E. .

CURRENT OPINION IN PHARMACOLOGY, 2008, 8 (02) :141-146

[9] Regulation of peripheral inflammation by spinal p38 MAP kinase in rats [J].

Boyle, David L. ;

Jones, Toni L. ;

Hammaker, Deepa ;

Svensson, Camille I. ;

Rosengren, Sanna ;

Albani, Salvatore ;

Sorkin, Linda ;

Firestein, Gary S. .

PLOS MEDICINE, 2006, 3 (09) :1616-1624

[10] p38 MAPK in development and cancer [J].

Bradham, Cynthia ;

McClay, David R. .

CELL CYCLE, 2006, 5 (08) :824-828

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