In this study, we tested two pharmacological inhibitors of PDK1, BX795 and BX912, to assess the role of Thr308 phosphorylation on Akt. PAR4-induced phosphorylation of Akt onThr308 was inhibited by BX795 without affecting phosphorylation of Akt on Ser473.

For example, the triphosphate form (PI (3,4,5)P 3) binds Akt and phosphoinositide-dependent kinase 1 (PDK1) so they accumulate in close proximity at the membrane. [1][10] Akt resides in the cytosol in an inactive conformation, until the cell is stimulated and it …

Jun 1, 2020 · Key findings: HCN1 expression and AKT phosphorylation at the Thr308 site were significantly decreased in atrial myocytes after PDK1 knockout or inhibition; in contrast, HCN2 and HCN4 levels were significantly increased.

Aug 8, 2016 · Castel et al. show that PDK1 activates SGK1 to phosphorylate and inhibit TSC2, contributing to maintenance of mTORC1 activity and resistance of PIK3CA-mutant cancer cells to PI3Kα inhibition. Targeting either PDK1 or SGK1 restores the sensitivity of these resistant cancer cells to PI3Kα inhibition.

Apr 6, 2022 · We propose a model of lipid-dependent PDK1 activation in which PH domain-mediated autoinhibition is relieved by PIP 3 or PI (3,4)P 2 binding, leading to strongly cooperative kinase domain...

Mar 22, 2022 · Here we report that ribosomal protein S6 kinase beta 1 (S6K1), a member of AGC kinases and downstream target of mechanistic target of rapamycin complex 1 (mTORC1), directly phosphorylates...

Oct 19, 2008 · Here we show that Rac1 stimulates a second, kinase-independent function of PAK1. The PAK1 kinase domain serves as a scaffold to facilitate Akt stimulation by PDK1 and to aid recruitment of Akt to...

Nov 6, 2012 · We report that nuclear PDK1 promoted cell proliferation by suppressing FOXO3A-dependent transcription of the gene encoding p27 Kip1 (an inhibitor of cell cycle progression), whereas it enhanced cell survival by inhibiting the activation of c-Jun amino-terminal kinase.

Mar 3, 2014 · In this study, we tested two pharmacological inhibitors of PDK1, BX795 and BX912, to assess the role of Thr308 phosphorylation on Akt. PAR4-induced phosphorylation of Akt on Thr308 was inhibited by BX795 without affecting phosphorylation of Akt on Ser473.

Jun 1, 2020 · The PDK1 inhibitor (GSK) and AKT activator (SC79) were used to identify the effects of the PDK1 − AKT signal pathway on the HCNs of atrial myocytes in PDK1 heart-specific knockout mice. We found that GSK could increase the mRNA level of HCN1, HCN2, and HCN4 by 2.16 times, 1.90 times, and 1.85 times, respectively ( Fig. 3 A–C ) (p < 0.05).