PI 3-kinase inhibition: a therapeutic target for respiratory disease

被引:42
作者
Finan, PM [1 ]
Thomas, MJ [1 ]
机构
[1] Novartis Horsham Res Ctr, Horsham RH12 5AB, W Sussex, England
关键词
asthma; chronic obstructive pulmonary disease (COPD); lymphocyte; mast cell; neutrophil; phosphoinositide 3-kinase (PI 3-kinase);
D O I
10.1042/BST0320378
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
Asthma and COPD (chronic obstructive pulmonary disease) are a growing major health burden, which, despite improvements in disease management, still require new effective treatments. As our understanding of the cellular and molecular processes which govern respiratory diseases improves, the range of potential therapeutic targets increase. PI 3-kinases (phosphoinositide 3-kinases) are a family of closely related enzymes, which play pivotal roles in a diverse array of cellular mechanisms. in the present paper, we review the evidence for PI 3-kinase involvement in various cellular processes underlying asthma and COPD generated through inhibitor studies and gene-targeting approaches, and discuss the prospects for PI 3 3-kinase inhibition as a future therapeutic strategy for the treatment of respiratory disease.
引用
收藏
页码:378 / 382
页数:5
相关论文
共 48 条
[1]   WORTMANNIN IS A POTENT PHOSPHATIDYLINOSITOL 3-KINASE INHIBITOR - THE ROLE OF PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE IN NEUTROPHIL RESPONSES [J].
ARCARO, A ;
WYMANN, MP .
BIOCHEMICAL JOURNAL, 1993, 296 :297-301
[2]   WORTMANNIN BLOCKS LIPID AND PROTEIN-KINASE ACTIVITIES ASSOCIATED WITH PI-3-KINASE AND INHIBITS A SUBSET OF RESPONSES INDUCED BY FC-EPSILON-R1 CROSS-LINKING [J].
BARKER, SA ;
CALDWELL, KK ;
HALL, A ;
MARTINEZ, AM ;
PFEIFFER, JR ;
OLIVER, JM ;
WILSON, BS .
MOLECULAR BIOLOGY OF THE CELL, 1995, 6 (09) :1145-1158
[3]   Wortmannin-sensitive phosphorylation, translocation, and activation of PLCγ1, but not PLCγ2, in antigen-stimulated RBL-2H3 mast cells [J].
Barker, SA ;
Caldwell, KK ;
Pfeiffer, JR ;
Wilson, BS .
MOLECULAR BIOLOGY OF THE CELL, 1998, 9 (02) :483-496
[4]   Chronic obstructive pulmonary disease: molecular and cellular mechanisms [J].
Barnes, PJ ;
Shapiro, SD ;
Pauwels, RA .
EUROPEAN RESPIRATORY JOURNAL, 2003, 22 (04) :672-688
[5]   A chemical compass [J].
Bourne, HR ;
Weiner, O .
NATURE, 2002, 419 (6902) :21-21
[6]   Phosphoinositide 3-kinase facilitates antigen-stimulated Ca2+ influx in RBL-2H3 mast cells via a phosphatidylinositol 3,4,5-trisphosphate-sensitive Ca2+ entry mechanism [J].
Ching, TT ;
Hsu, AL ;
Johnson, AJ ;
Chen, CS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (18) :14814-14820
[7]   A crucial role for the p110δ subunit of phosphatidylinositol 3-kinase in B cell development and activation [J].
Clayton, E ;
Bardi, G ;
Bell, SE ;
Chantry, D ;
Downes, CP ;
Gray, A ;
Humphries, LA ;
Rawlings, D ;
Reynolds, H ;
Vigorito, E ;
Turner, M .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 196 (06) :753-763
[8]  
Coffer PJ, 1998, BIOCHEM J, V329, P121
[9]   Role of PI3-kinase-dependent Bad phosphorylation and altered transcription in cytokine-mediated neutrophil survival [J].
Cowburn, AS ;
Cadwallader, KA ;
Reed, BJ ;
Farahi, N ;
Chilvers, ER .
BLOOD, 2002, 100 (07) :2607-2616
[10]  
Cozier GE, 2004, CURR TOP MICROBIOL, V282, P49