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• W2066063721 abstract "Studies were carried out to examine the role of the major insulin receptor tyrosine autophosphorylation sites in stimulation of S6 kinase activity. For these studies, we employed HTC rat hepatoma cells transfected with and expressing human insulin receptors. In cells transfected with and expressing a large number of normal human insulin receptors (HTC-IR cells), the sensitivity of cells to insulin to stimulate S6 kinase was increased tenfold when compared to untransfected wild type HTC cells (HTC-WT cells). However, in cells transfected with and expressing a large number of mutated human insulin receptors where the tyrosines at three major autophosphorylation sites (1158, 1162, and 1163) were mutated to phenylalanines (HTC-F3 cells), there was no change in insulin sensitivity when compared to HTC-WT cells. We next studied the effect of a human-specific monoclonal antbody to the human insulin receptor, MA-5, on S6 kinase activation. In HTC-WT cells, MA-5 did not interact with endogenous rat insulin receptors and thus did not stimulate S6 kinase. In HTC-IR cells expressing normal human insulin receptors, MA-5 stimulated S6 kinase. Interestingly, MA-5, unlike insulin, was also able to stimulate S6 kinase in HTC-F3 cells expressing mutated receptors. In order to further understand the signaling mechanisms by MA-5 and insulin, two potential intermediate protein kinases were investigate. Neither insulin nor MA-5 appears to activate either microtubule-associated protein 2 (MAP-2) kinase or protein kinase C in these cells. These studies suggest therefore that: 1) insulin and MA-5 may signal S6 kinase activation by independent mechanisms that do not employ either MAP-2 kinase or protein kinase C; and 2) under certain circumstances, S6 kinase appears to be activated by mechanisms that are independent of insulin receptor tyrosine autophosphorylation." @default.
• W2066063721 created "2016-06-24" @default.
• W2066063721 creator A5086397090 @default.
• W2066063721 date "1992-03-01" @default.
• W2066063721 modified "2023-10-14" @default.
• W2066063721 title "Monoclonal antibody to the human insulin receptor, but not insulin, stimulates S6 kinase via human insulin receptors mutated at three major tyrosine autophosphorylation sites" @default.
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• W2066063721 doi "https://doi.org/10.1002/jcb.240480313" @default.
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• W2066063721 hasPublicationYear "1992" @default.
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