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PRKCA inhibits AKT. 21 / 22
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"Importantly, PKCalpha signaling was able to suppress AKT activity even in the face of further activation of the pathway."
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"Remarkably, knockdown of PKCalpha in cells with genetic hyperactivation of the PI3K and AKT pathway further enhanced the activity of AKT, highlighting the ability of PKCalpha deficiency to contribute to the strength of PI3K and AKT signaling in EC cells."
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"As discussed above, inhibition of AKT by PKCα in HeLa cells destabilized the de-ubiquitinase, USP8, leading to enhanced ubiquitination and degradation of EGFR ( xref )."
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"Given that Akt activation is PKCalpha dependent, we next examined whether the expression of a membrane targeted form of PKCalpha (myrPKCalpha) could rescue Akt activation in S4 -/- endothelial cells."
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"Remarkably, PKCalpha knockdown also upregulated basal AKT activity in HEC-6 and SNG-M cells, two PTEN mutant cell lines that naturally harbor coincident mutations in the catalytic (PIK3CA) or regulato[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"This effect is consistent with the known inhibition of Akt by PKCα ( xref ), the only cPKC expressed in these cells ( xref )."
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"Future studies will explore the specific PP2A family members involved as well as the specific holoenzyme complex(es) responsible for mediating PKCα-induced inactivation of AKT."
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"Remarkably, PKCalpha knockdown also upregulated basal AKT activity in HEC-6 and SNG-M cells, two PTEN mutant cell lines that naturally harbor coincident mutations in the catalytic (PIK3CA) or regulatory (PIK3R1) subunits of PI3K, respectively (XREF_FIG, middle and right panels; also see XREF_FIG, compare lane 1 with lanes 3-6 in both panels)."
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"It is conceived that presence of obesity-induced DAG accumulation in the heart signified the development of cardiac insulin resistance through PKCα-dependent inhibition of Akt, p70s6k activation, and IRS-1 Ser332/336 phosphorylation (496)."
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"Together, these results indicate that PKCalpha inhibits PI3K and AKT signaling through a PHLPP independent, PP2A-family-dependent mechanism."
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"PKCα-induced AKT inactivation may involve direct effects of PP2A family phosphatases on activating phosphorylation at T308 and S473 ( Manning and Toker, 2017 ), although potential effects on upstream [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Here, we demonstrate that PKCalpha activates the serine/threonine phosphatase PP2A in EC cells and inactivates AKT via a PP2A- or PP2A like phosphatase dependent mechanism."
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"PKCα-induced AKT inactivation may involve direct effects of PP2A family phosphatases on activating phosphorylation at T308 and S473 ( xref ), although potential effects on upstream regulators of AKT activity remain to be formally excluded ( xref ). (It should be noted that although PP2A may preferentially dephosphorylate AKT on the T308 site, it can also dephosphorylate AKT on the S473 site, as described in a variety of biological systems [ xref ].) A role of PP2A in the antitumor effects of PKCα in the endometrium is consistent with known functions of the phosphatase as a bona fide tumor suppressor, with key activities in maintenance of cellular homeostasis ( xref )."
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"These findings, together with the demonstration that agonist induced PKCalpha activation suppresses AKT in EC cells, identify PKCalpha as an inhibitor of PI3K and AKT signaling in the endometrium that is capable of disabling the AKT oncoprotein, even in the context of multiple activating mutations in upstream signaling intermediates (e.g., PTEN and PIK3CA in HEC-251 cells and PTEN, PIK3CA, and KRAS in SNG-M cells)."
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"PKCalpha Activity Inhibits PI3K and AKT Signaling in EC Cells via a PHLPP-1/2-Independent, PP2A-Family-Dependent Mechanism."
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"Meanwhile, decreased Akt activity and PKCalpha, Ras, and NF-kappaB protein expressions were detected in dose dependent manners."
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"Together, these results indicate that PKCalpha inhibits PI3K and AKT signaling through a PHLPP independent, PP2A-family-dependent mechanism.While universal loss of PKCalpha was seen in uterine lesions[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Based on the findings of a previous study using myeloid progenitor cells [XREF_BIBR], we hypothesized that the BNTX induced suppression of PKCalpha activity causes AKT inactivation."
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"A study showed that PKCalpha can suppress AKT activity through a protein phosphatase 2A ( PP2A ) - dependent mechanism [ 78 ] ."
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"As discussed above , inhibition of AKT by PKCalpha in HeLa cells destabilized the de-ubiquitinase , USP8 , leading to enhanced ubiquitination and degradation of EGFR ( Cai et al ., 2010 ) ."
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"In mouse muscle and adipose tissues, knockout of Prkca (encoding PKCalpha) enhances IRS1 and PIK3 --> AKT and aPKC signalling, as well as glucose transport [XREF_BIBR]."
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