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- _6 value "Tyrosine phosphorylation of IRS-1, as well as its association with p85{alpha} and activation of IRS-1-associated PI 3-kinase activity, decreased after 15-30 min of insulin stimulation in PTP1B+/+ neonatal hepatocytes (Fig. 4, upper panel). In sharp contrast, the effect of insulin on IRS-1 tyrosine phosphorylation in PTP1B-/- neonatal hepatocytes was prolonged; tyrosine phosphorylation of IRS-1, IRS-1/p85{alpha} association, and IRS-1-associated PI 3-kinase activity was sustained for 4 h in PTP1B-/- neonatal hepatocytes (Fig. 4, lower panel). Similar to findings for IRS-1, IRS-2 tyrosine phosphorylation, its binding to p85{alpha}, and activation of IRS-2-associated PI 3-kinase activity decreased between 15 and 60 min in insulin-stimulated PTP1B+/+ neonatal hepatocytes (Fig. 5, upper panel). However, insulin action was prolonged up to 4 h on this signaling pathway in PTP1B-/- neonatal hepatocytes (Fig. 5, lower panel). " provenance.