Cellular function of phosphoinositide 3-kinases: Implications for development, immunity, homeostasis, and cancer

Citation
R. Katso et al., Cellular function of phosphoinositide 3-kinases: Implications for development, immunity, homeostasis, and cancer, ANN R C DEV, 17, 2001, pp. 615-675
Citations number
344
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Cell & Developmental Biology
Journal title
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY
ISSN journal
1081-0706 → ACNP
Volume
17
Year of publication
2001
Pages
615 - 675
Database
ISI
SICI code
1081-0706(2001)17:<615:CFOP3I>2.0.ZU;2-1
Abstract
The phosphoinositide 3-kinase (PI3K) family of enzymes is recruited upon gr owth factor receptor activation and produces 3' phosphoinositide lipids. Th e lipid products of PI3K act as second messengers by binding to and activat ing diverse cellular target proteins. These events constitute the start of a complex signaling cascade, which ultimately results in the mediation of c ellular activities such as proliferation, differentiation, chemotaxis, surv ival, trafficking, and glucose homeostasis. Therefore, PI3Ks play a central role in many cellular functions. The factors that determine which cellular function is mediated are complex and may be partly attributed to the diver sity that exists at each level of the PI3K signaling cascade, such as the t ype of stimulus, the isoform of PI3K, or the nature of the second messenger lipids. Numerous studies have helped to elucidate some of the key factors that determine cell fate in the context of PI3K signaling. For example, the past two years has seen the publication of many transgenic and knockout mo use studies where either PI3K or its signaling components are deregulated. These models have helped to build a picture of the role of PI3K in physiolo gy and indeed there have been a number of surprises. This review uses such models as a framework to build a profile of PI3K function within both the c ell and the organism and focuses, in particular, on the role of PI3K in cel l regulation, immunity, and development. The evidence for the role of dereg ulated PI3K signaling in diseases such as cancer and diabetes is reviewed.