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PTEN leads to the phosphorylation of IRS1. 6 / 6
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"Along these lines, Weng et al. have demonstrated that PTEN blocks MAPK phosphorylation in response to insulin stimulation by inhibiting phosphorylation of IRS-1 and the formation of the IRS-1/Grb2/Sos[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"The effect of TNF on insulin promoted tyrosine phosphorylation of IRS-1 was blocked by inhibition of PI 3-kinase and the PTEN tumor suppressor, which dephosphorylates the lipids that mediate PI 3-kinase functions, whereas constitutively active Akt impaired insulin promoted IRS-1 tyrosine phosphorylation."
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"Consistently with such feedback regulation, stable knockdown of PTEN enhanced IRS1 phosphorylation only minimally in NEDD4 −/− MEFs, although it substantially restored IGF1-induced AKT activation, presumably by suppressing the PIP3 phosphatase activity of PTEN ( xref )."
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"PTEN silencing increased the phosphorylation of AKT and the expression of PI3K but decreased the phosphorylation of IRS1, which increased the phosphorylation levels of glycogen synthase kinase-3beta (GSK-3beta) and expression of sterol regulatory element binding protein-1c (SREBP-1c)."
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"Moreover, PTEN inhibits insulin signaling by indirectly suppressing the phosphorylation of mitogen activated protein kinase (MAPK) and blocking insulin receptor substrate 1 (IRS-1) phosphorylation [XREF_BIBR]."
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"Our data suggest that PTEN blocks MAPK phosphorylation in response to insulin stimulation by inhibiting the phosphorylation of IRS-1 and IRS-1, Grb2, and Sos complex formation, which leads to downregulation of cyclin D1, inhibition of cell cycle progression and suppression of cell growth."
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