IndraLab

Statements

AKT phosphorylates GSK3 on S21. 41 / 41
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"Growth factors, such as EGF, result in inactivation of GSK3 through Ser9 phosphorylation of GSK3α or Ser21 phosphorylation of GSK3β by AKT ."
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"The most well-defined regulatory mechanism is by phosphorylation of serine-9 in GSK-3β or serine-21 in GSK-3α, which inhibits GSK-3 activity [20-22]. The Akt signaling pathway often is a major regulator of GSK-3 because Akt phosphorylates GSK-3 on these inhibitory serine residues, which has been shown to involved in dopamine signaling and many aspects of psychiatric disorders [23]."
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"Leptin stimulation of rat arcuate increases PKB phosphorylation with subsequent GSK3 phosphorylation at Ser-9/Ser-21 (13), actions also reported for leptin on mouse skeletal muscle cells (32, 33), mouse cortical neurons (34), and MCF-7 breast cancer cells (35). These latter actions of leptin replicate those of insulin, which increases PI3K activity and raises PtdIns(3,4,5)P3 levels with subsequent increased PKB and GSK3 phosphorylation (5). Importantly, the phosphorylation of GSK3 at these serine residues by PKB is associated with reduced kinase activity (36, 37)."
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"Further, Akt phosphorylates GSK-3 (Ser 21 in GSK-3 α and Ser 9 in GSK-3 β) and suppresses its action, allowing normal cell growth and survival to persist ( Wee and Wang, 2017 )."
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"GSK3 is one of the main targets of Akt and is phosphorylated by active Akt at its two subunits GSK3α (Ser21) and GSK3β (Ser9) ( Manning and Toker, 2017 )."
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"Akt phosphorylates GSK-3 at Serine 21 and Serine 9 in two different isoforms GSK-3 and GSK-3 respectively and inhibits its activity [ xref , xref ]."
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"Recently, we generated homozygous knockin mice in which the PKB phosphorylation site on GSK3α (Ser21) and GSK3β (Ser9) was changed to Ala to prevent inactivation of this enzyme by insulin [5] ."
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"As GSK3 is phosphorylated, and hence inhibited, at Ser9/Ser21 by AKT ( Cohen and Frame, 2001 ), it is tempting to speculate that AKT counteracts CK2-dependent PTEN inactivation through this feedback m[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"We next studied the phosphorylation of the inhibitory PKB phosphorylation sites on GSK3α (Ser21) and GSK3β (Ser9) employing phospho-specific antibodies."
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"GSK3 is rapidly phosphorylated at Ser21 in GSK3α or Ser9 in GSK3β by AKT, resulting in inhibition of GSK3 kinase activity [ xref ]."
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"Phosphorylation of GSK3 by AKT at auto-inhibitory N-terminal serine residues (Ser9/Ser21) inhibits GSK3 activity."
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"PKB is known to phosphorylate GSK-3 at Ser 21 in GSK-3α and Ser 9 in GSK-3β."
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"GSK-3 is a substrate of Akt, which phosphorylates GSK-3 on Ser-21, thereby inactivating it ."
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"PKB/Akt phosphorylates GSK3α(Ser-21) and GSK3β(Ser-9), and these residues lie in a typical PKB/Akt consensus substrate motif [14] ."
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"Evidence of elevated mTOR phosphorylation on S2448 and elevated GSK3 phosphorylation at both S9 and S21, which are all known Akt phosphorylation sites, was also detected in NIC/LKB1fl/fl tumors (Figure 4A)."
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"More recently, GSK3 was shown to enhance proteasomal degradation of VEGFR-2 by regulating the binding of β-transducin repeats containing E3 ubiquitin protein ligase to VEGFR-2 (29), and GSK3 activity is inhibited by AKT that phosphorylates the serine residues Ser21 in GSK3α and Ser9 in GSK3β (30)."
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"AKT phosphorylates GSK3 α or β at Ser21 or Ser9 residue respectively."
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"Akt can phosphorylate GSK3α and GSK3β at residues S21 and S9, respectively, thereby inactivating GSK3 and suppressing β-catenin degradation [144–146]."
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"Furthermore, activated Akt and PKB can induce serine phosphorylation of GSK3 (Ser21 for GSK3alpha; Ser9 for GSK3beta) to inactivate the kinase activity, which subsequently lead to an activation of GS and then increased glycogen synthesis [XREF_BIBR, XREF_BIBR]."
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"We found that Ser 21/9 phosphorylation of GSK-3 was mediated by Ca (2+)/calmodulin-dependent protein kinase II (CaMKII) but not by Akt and PKB, PKA, or p90 (RSK)."
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"For instance, two pancreatic cancer cell lines, PANC1 and ASPC1, exhibit amplification of AKT and high levels of AKT RNA and protein [XREF_BIBR] but also highly active GSK-3beta suggesting that, although some pools of GSK-3 can be phosphorylated by AKT at Ser21 and Ser9 and inhibited, other pools of GSK-3 may remain active in cancer cells [XREF_BIBR]."
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"Akt phosphorylates GSK3β at Ser21 and Ser9 and thereby inactivates this protein kinase."
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"Stimulation of N29/4 cells by insulin for 30 min results in a substantial inhibition of GSK3 activity, as expected from increased PKB activity causing GSK3 Ser-9 and Ser-21 phosphorylation."
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"GSK3 is rapidly phosphorylated at Ser21 in GSK3α or Ser9 in GSK3β by AKT, resulting in inhibition of GSK3 kinase activity [40]."
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"For instance, two pancreatic cancer cell lines, PANC1 and ASPC1, exhibit amplification of AKT and high levels of AKT RNA and protein [43] but also highly active GSK-3β suggesting that, although some pools of GSK-3 can be phosphorylated by AKT at Ser21/Ser9 and inhibited, other pools of GSK-3 may remain active in cancer cells [31]."
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"Noteworthy, while activated AKT inhibits GSK-3 through the phosphorylation of GSK-3 at Ser21/Ser9, however, such inactivation does not always affect β-catenin levels in the cell and does not completely inhibit GSK-3."
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"Due to the indispensable role of Akt in cancer and activity inhibiting GSK-3 phosphorylation by Akt at its Ser21/9 residue, suppression of GSK-3 activity was assumed to be tumor promoting."
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"By contrast, the high-salt diet did not significantly affect Akt expression or its Ser 473 phosphorylation in soleus muscle.GSK-3 is a substrate of Akt, which phosphorylates GSK-3 on Ser 21, thereby i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"GSK-3 serine kinase is directly phosphorylated by Akt on Ser-9 (α-isoform) or Ser-21 (β-isoform), leading to inactivation of GSK-3 kinase ( Laviola et al., 2001 )."
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"Additionally, Akt phosphorylation inhibits the two isoforms of GSK3 in response to growth factors and hormones, including BDNF, IGF, and insulin (Yamada et al., 2002; Altar et al., 2008). Specifically, Akt phosphorylates specific residues serine 21 for GSK3α and serine 9 for GSK3β that are located in the N-terminal domains of both GSK3 isoforms (Stambolic and Woodgett, 1994; Frame and Cohen, 2001)."
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"Furthermore, activated Akt and PKB can induce serine phosphorylation of GSK3 (Ser21 for GSK3alpha; Ser9 for GSK3beta) to inactivate the kinase activity, which subsequently lead to an activation of GS and then increased glycogen synthesis [XREF_BIBR, XREF_BIBR]."
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"Akt phosphorylates Ser21 of GSK3α and Ser9 of GSK3β resulting in transient inactivation of GSK3β [22, 23]."
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"The activation of AKT causes phosphorylation of GSK3α (Ser 21) and GSK3β (Ser 9) and suppresses their activities."
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"The phosphorylation of GSK-3 by AKT at serine 21 in GSK-3α or serine 9 in GSK-3β inhibits the kinase activity of GSK-3 [ xref , xref ]."
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"This is not surprising as GSK-3α/β isoforms are phosphorylated directly by AKT on S21 and S9 (α and β isoforms respectively), leading to GSK-3 inhibition ."
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"Similarly, mutation of two Akt phosphorylation sites on GSK3 (S9 and S21) to alanine prevents inhibition of GSK3 and results in impaired insulin-stimulated glycogen synthesis [128]."
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"Activated AKT can then phosphorylate the two GSK3 isoforms on their N-terminus (at Ser21 for GSK3α and Ser9 for GSK3β), inactivating them [37, 38]."
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"Li is a monovalent cation that is capable of inhibiting GSK3 both directly, via competition with its cofactor magnesium, and indirectly, via activation of the PI3K/Akt pathway, which phosphorylates GSK3 at the Ser 21 (GSK3α) and Ser 9 (GSK3β) sites, preventing substrate binding to the GSK3 isoforms (Hamstra, Whitley, et al., 2020)."
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"GSK3 is rapidly phosphorylated at Ser21 in GSK3alpha or Ser9 in GSK3beta by AKT, resulting in inhibition of GSK3 kinase activity [XREF_BIBR]."
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"PKB and Akt can phosphorylate both GSK3 isoforms (S21 of GSK3alpha and S9 of GSK3beta), leading to an inhibition of GSK3 activity."
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"PKB and Akt can phosphorylate both GSK3 isoforms (S21 of GSK3alpha and S9 of GSK3beta), leading to an inhibition of GSK3 activity."
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