Nov 7, 2011 · We found, unexpectedly, that a protein called glycogen synthase kinase-3 (GSK-3) plays a role in S6K1 regulation. This study contradicts concerns that GSK-3 inhibition, a promising drug target for diabetes and other major illnesses, would promote tumor growth.

GSK-3 role in autophagy regulation has been studied in the past few years. GSK-3 inhibits autophagy through the mammalian target of rapamycin (mTOR) complex 1 (mTORC1). In fact, overexpression of either GSK-3α or GSK-3β activates mTORC1 and suppresses autophagy in MCF-7 breast cancer cells.

The GSK-3 signaling pathway was reported to regulate autophagy flux via the mTORC1, PKC and AKT signaling pathways [30,61,65,78,111]. mTORC1, known as a major autophagy regulator, is involved in the phosphorylation and inhibition of GSK-3β via its substrate, S6K [58,59].

Apr 1, 2020 · GSK3 is emerging as a major player orchestrating resistance to mTOR-targeted therapeutics. The introduction of therapeutics targeting specific tumor-promoting oncogenic or non-oncogenic signaling pathways has revolutionized cancer treatment.

Nov 1, 2006 · Here we measured the amount of phospho-Akt and several of its downstream anabolic targets (glycogen synthase kinase-3beta (GSK-3beta), mTOR, p70 (s6k) and 4E-BP1) and catabolic targets (Foxo1, Foxo3, atrogin-1 and MuRF1).

We have characterized a short peptide derived from the GSK-3 interaction domain of Axin that potently inhibits GSK-3 activity in vitro and in mammalian cells and robustly activates Wnt-dependent transcription, mimicking lithium action.

Amino acids potently stimulate p70(S6K), and recent studies on cultured muscle cells suggest that amino acids also inactivate GSK-3 and/or activate GS via activating p70(S6K).

Nov 22, 2011 · The p70 ribosomal protein S6 kinase 1 (S6K1) plays a key role in cell growth and proliferation by regulating insulin sensitivity, metabolism, protein synthesis, and cell cycle. Thus, deregulation of S6K contributes to the progression of type 2 diabetes, obesity, aging, and cancer.

Second, we unexpectedly found that glycogen syn-thase kinase (GSK)-3 promotes turn motif phosphorylation. Our studies show that mammalian target of rapamycin and GSK-3 cooperate to control the activity of S6K1, an important regulator of cell proliferation and growth.

Sep 29, 2015 · Signal pathway study of MK-2206 non-resistant cells showed that AKT acted in mTOR-S6K dependent method (LAN-1 and SK-N-DZ), in which inhibition of AKT reduced activity of mTOR-S6K signaling; and mTOR-S6K independent method (KP-N-SIFA and NB-19), in which inhibition of AKT did not impair the activity of mTOR-S6K signaling.