Journal
EXPERT OPINION ON THERAPEUTIC TARGETS
Volume 14, Issue 7, Pages 703-725Publisher
INFORMA HEALTHCARE
DOI: 10.1517/14728222.2010.492779
Keywords
allergy; angiogenesis; cancer; p21-activated kinases; Rho GTPases; signal transduction
Categories
Funding
- National Institute of Health [CA098176, CA1337708, CA116060]
- American Heart Association [0830326N]
- University of Georgia Research Foundation
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Importance of the field: P21-activated kinases (PAKs) are involved in multiple signal transduction pathways in mammalian cells. PAKs, and PAK1 in particular, play a role in such disorders as cancer, mental retardation and allergy. Cell motility, survival and proliferation, the organization and function of cytoskeleton and extracellular matrix, transcription and translation are among the processes affected by PAK1. Areas covered in this review: We discuss the mechanisms that control PAK1 activity, its involvement in physiological and pathophysiological processes, the benefits and the drawbacks of the current tools to regulate PAK1 activity, the evidence that suggests PAK1 as a therapeutic target and the likely directions of future research. What the reader will gain: The reader will gain a better knowledge and understanding of the areas described above. Take home message: PAK1 is a promising therapeutic target in cancer and allergen-induced disorders. Its suitability as a target in vascular, neurological and infectious diseases remains ambiguous. Further advancement of this field requires progress on such issues as the development of specific and clinically acceptable inhibitors, the choice between targeting one or multiple PAK isoforms, elucidation of the individual roles of PAK1 targets and the mechanisms that may circumvent inhibition of PAK1.
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