Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Sci. Signal., 17 August 2010
Vol. 3, Issue 135, p. re5
[DOI: 10.1126/scisignal.3135re5]

REVIEWS

Phosphatidylinositol 3-Kinase Signaling in Thymocytes: The Need for Stringent Control

Elisabeth Fayard1*, Gerald Moncayo1, Brian A. Hemmings1*, and Georg A. Holländer2

1 Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
2 Pediatric Immunology, Center for Biomedicine, Department of Clinical-Biological Sciences, The University of Basel and The University Children’s Hospital, Mattenstrasse 28, CH-4058 Basel, Switzerland.

Abstract: The thymus serves as the primary site for the lifelong formation of new T lymphocytes; hence, it is essential for the maintenance of an effective immune system. Although thymocyte development has been widely studied, the mechanisms involved are incompletely defined. A comprehensive understanding of the molecular events that control regular thymocyte development will not only shed light on the physiological control of T cell differentiation but also probably provide insight into the pathophysiology of T cell immunodeficiencies, the molecular basis that underpins autoimmunity, and the mechanisms that instigate the formation of T cell lymphomas. Phosphatidylinositol 3-kinases (PI3Ks) play a critical role in thymocyte development, although not all of their downstream mediators have yet been identified. Here, we discuss experimental evidence that argues for a critical role of the PI3K-phosphoinositide–dependent protein kinase (PDK1)–protein kinase B (PKB) signaling pathway in the development of both normal and malignant thymocytes, and we highlight molecules that can potentially be targeted therapeutically.

* Corresponding authors. E-mail: brian.hemmings{at}fmi.ch (B.A.H.); elisabeth.fayard{at}fmi.ch (E.F.)

Citation: E. Fayard, G. Moncayo, B. A. Hemmings, G. A. Holländer, Phosphatidylinositol 3-Kinase Signaling in Thymocytes: The Need for Stringent Control. Sci. Signal. 3, re5 (2010).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Transition from Heterotypic to Homotypic PDK1 Homodimerization Is Essential for TCR-Mediated NF-{kappa}B Activation.
J.-A. Kang, S. P. Jeong, D. Park, M. S. Hayden, S. Ghosh, and S.-G. Park (2013)
J. Immunol. 190, 4508-4515
   Abstract »    Full Text »    PDF »
KAP1 regulates gene networks controlling T-cell development and responsiveness.
F. R. Santoni de Sio, I. Barde, S. Offner, A. Kapopoulou, A. Corsinotti, K. Bojkowska, R. Genolet, J. H. Thomas, I. F. Luescher, D. Pinschewer, et al. (2012)
FASEB J 26, 4561-4575
   Abstract »    Full Text »    PDF »
The Novel Therapeutic Effect of Phosphoinositide 3-Kinase-{gamma} Inhibitor AS605240 in Autoimmune Diabetes.
J. Azzi, R. F. Moore, W. Elyaman, M. Mounayar, N. El Haddad, S. Yang, M. Jurewicz, A. Takakura, A. Petrelli, P. Fiorina, et al. (2012)
Diabetes 61, 1509-1518
   Abstract »    Full Text »    PDF »
Structural Basis for Activation and Inhibition of Class I Phosphoinositide 3-Kinases.
O. Vadas, J. E. Burke, X. Zhang, A. Berndt, and R. L. Williams (2011)
Science Signaling 4, re2
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882