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...

PDK1 activates S6K, SGK and PKB isoforms by phosphorylating these kinases at their T-loop. We demonstrate that a pocket in the kinase domain of PDK1, termed the ‘PIF-binding pocket’, plays a key role in mediating the interaction and phosphorylation of S6K1 and SGK1 at their T-loop motif by PDK1.

Thr389 phosphorylation promotes docking of phosphatidyl-inositide dependent kinase 1 (PDK1), which phosphorylates S6K at T229. Phosphorylation of T389 and T229 results in full activation of S6K [ 18 ].

Dec 12, 2001 · Here we show that, in Drosophila, dPDK1 controls cellular and organism growth by activating dAkt and S6 kinase, dS6K. Furthermore, dPDK1 genetically interacts with dRSK but not with dPKN, encoding two substrates of PDK1 in vitro.

Jan 30, 1998 · A regulatory link between p70 s6k and PKB was demonstrated, as PDK1 was found to selectively phosphorylate p70 s6k at Thr 229. More importantly, PDK1 activated p70 s6k in vitro and in vivo, whereas the catalytically inactive PDK1 blocked insulin-induced activation of …

Aug 15, 2001 · PDK1 activates S6K, SGK and PKB isoforms by phosphorylating these kinases at their T-loop. We demonstrate that a pocket in the kinase domain of PDK1, termed the 'PIF-binding pocket', plays a key role in mediating the interaction and phosphorylation of S6K1 and SGK1 at their T-loop motif by PDK1.

We provide genetic evidence that PDK1 is essential for mouse embryonic development, and regulates cell size independently of cell number or proliferation, as well as insulin’s ability to activate PKB, S6K and RSK. Keywords: cell growth/cell size/embryonic development/PDK1/PKB–Akt/PI 3-kinase.

Here we report that, as a bona fide substrate of S6K1, PDK1 could be phosphorylated at its C-terminal PH domain, which is critical for recruiting the adaptor protein 14-3-3 to interact with...

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 PDK1 at its pleckstrin homology (PH) domain, and impairs PDK1 interaction with and activation of AKT.

Aug 8, 2016 · Here we show that in cancer cells resistant to PI3Kα inhibition, PDK1 blockade restores sensitivity to these therapies. SGK1, which is activated by PDK1, contributes to the maintenance of residual mTORC1 activity through direct phosphorylation and inhibition of TSC2.