Targeting kinases in asthma.
Through a regulation cascade via the site-specific phosphorylation of downstream substrates, members of kinase signaling pathways play multiple cellular regulatory roles. Because of the contribution of kinases in a diverse number of cellular processes, members of these pathways have become attractive targets for rational drug design. Members of these kinase signalling families, such as mitogen-activated kinases, tyrosine kinases (receptor and non-receptor) and ras human orthologue kinases among others have been shown to play key roles in the pathogenesis of immune, inflammatory and remodelling events that occur during asthma. This review highlights, through information that has been obtained from transgenic and knockout systems, small-molecule inhibitors and antisense technology, the role of select members of kinase families in the pathogenesis of asthma, and discusses the rationale for developing specific inhibitors of these kinases for the treatment of asthma.
Blease
Kate
K
Celgene, 4550 Towne Centre Court, San Diego, CA 92121, USA. kblease@celgene.com
D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000201:enzymology*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D047428:Protein Kinase Inhibitors; D011494:Protein Kinases