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.


Sci. STKE, 23 January 2001
Vol. 2001, Issue 66, p. pe1
[DOI: 10.1126/stke.2001.66.pe1]


PDK2: A Complex Tail in One Akt

Tung O. Chan and Philip N. Tsichlis

The authors are at the Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA. E-mail: P_Tsichlis{at}

Abstract: The kinase Akt contains two phosphatidylinositol-3 kinase (PI3K)-dependent phosphorylation sites, one in the activation loop (Thr308) and one in the carboxyl-terminal tail (Ser473), both of which are conserved among the members of the AGC kinase family. Under physiological conditions, the phosphorylation of Thr308 appears to be coordinately regulated with the phosphorylation of Ser473. Under experimental conditions, however, the two sites can be uncoupled, suggesting that their phosphorylation is controlled by different kinases and phosphatases. Phosphoinositide-dependent kinase 1 (PDK1), the kinase that phosphorylates the activation loop site, has been unambiguously identified. However, PDK2, a kinase that is hypothesized to phosphorylate the hydrophobic carboxyl-terminal site, remains elusive. This Perspective examines the regulation and biological significance of Akt phosphorylation at Ser473. The authors propose that Ser473 undergoes both autophosphorylation and phosphorylation by other kinases. Both events may be promoted by interactions between PDK1 and phosphorylated or phosphomimetically altered hydrophobic phosphorylation motifs in kinases associated with Akt. These interactions may induce conformational changes in Akt that make Ser473 accessible to phosphorylation.

Citation: T. O. Chan, P. N. Tsichlis, PDK2: A Complex Tail in One Akt. Sci. STKE 2001, pe1 (2001).

Read the Full Text

Genetic loss of SH2B3 in acute lymphoblastic leukemia.
A. Perez-Garcia, A. Ambesi-Impiombato, M. Hadler, I. Rigo, C. A. LeDuc, K. Kelly, C. Jalas, E. Paietta, J. Racevskis, J. M. Rowe, et al. (2013)
Blood 122, 2425-2432
   Abstract »    Full Text »    PDF »
Regulation of alveolar macrophage p40phox: hierarchy of activating kinases and their inhibition by PGE2.
E. Bourdonnay, C. H. Serezani, D. M. Aronoff, and M. Peters-Golden (2012)
J. Leukoc. Biol. 92, 219-231
   Abstract »    Full Text »    PDF »
Vital roles of mTOR complex 2 in Notch-driven thymocyte differentiation and leukemia.
K. Lee, K. T. Nam, S. H. Cho, P. Gudapati, Y. Hwang, D.-S. Park, R. Potter, J. Chen, E. Volanakis, and M. Boothby (2012)
J. Exp. Med. 209, 713-728
   Abstract »    Full Text »    PDF »
A small-molecule inhibitor of D-cyclin transactivation displays preclinical efficacy in myeloma and leukemia via phosphoinositide 3-kinase pathway.
X. Mao, B. Cao, T. E. Wood, R. Hurren, J. Tong, X. Wang, W. Wang, J. Li, Y. Jin, W. Sun, et al. (2011)
Blood 117, 1986-1997
   Abstract »    Full Text »    PDF »
The PI3K/Akt/mTOR pathway is activated in murine lupus nephritis and downregulated by rapamycin.
K. Stylianou, I. Petrakis, V. Mavroeidi, S. Stratakis, E. Vardaki, K. Perakis, S. Stratigis, A. Passam, E. Papadogiorgaki, K. Giannakakis, et al. (2011)
Nephrol. Dial. Transplant. 26, 498-508
   Abstract »    Full Text »    PDF »
Development of light response and GABAergic excitation-to-inhibition switch in zebrafish retinal ganglion cells.
R.-w. Zhang, H.-p. Wei, Y.-m. Xia, and J.-l. Du (2010)
J. Physiol. 588, 2557-2569
   Abstract »    Full Text »    PDF »
Mechanism of Two Classes of Cancer Mutations in the Phosphoinositide 3-Kinase Catalytic Subunit.
N. Miled, Y. Yan, W.-C. Hon, O. Perisic, M. Zvelebil, Y. Inbar, D. Schneidman-Duhovny, H. J. Wolfson, J. M. Backer, and R. L. Williams (2007)
Science 317, 239-242
   Abstract »    Full Text »    PDF »
The p85 regulatory subunit of phosphoinositide 3-kinase down-regulates IRS-1 signaling via the formation of a sequestration complex.
J. Luo, S. J. Field, J. Y. Lee, J. A. Engelman, and L. C. Cantley (2005)
J. Cell Biol. 170, 455-464
   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