RT Journal Article
SR Electronic
T1 PDK2: A Complex Tail in One Akt
JF Science's STKE
JO Sci. STKE
FD American Association for the Advancement of Science
SP pe1
OP pe1
DO 10.1126/stke.2001.66.pe1
VO 2001
IS 66
A1 Chan, Tung O.
A1 Tsichlis, Philip N.
YR 2001
UL http://stke.sciencemag.org/content/2001/66/pe1.abstract
AB 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.