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Mol Cell Biol 2000, PMID: 10594015

IRS-4 mediates protein kinase B signaling during insulin stimulation without promoting antiapoptosis.

Uchida, T; Myers, M G; White, M F

Insulin receptor substrate (IRS) proteins are tyrosine phosphorylated and mediate multiple signals during activation of the receptors for insulin, insulin-like growth factor 1 (IGF-1), and various cytokines. In order to distinguish common and unique functions of IRS-1, IRS-2, and IRS-4, we expressed them individually in 32D myeloid progenitor cells containing the human insulin receptor (32D(IR)). Insulin promoted the association of Grb-2 with IRS-1 and IRS-4, whereas IRS-2 weakly bound Grb-2; consequently, IRS-1 and IRS-4 enhanced insulin-stimulated mitogen-activated protein kinase activity. During insulin stimulation, IRS-1 and IRS-2 strongly bound p85alpha/beta, which activated phosphatidylinositol (PI) 3-kinase, protein kinase B (PKB)/Akt, and p70(s6k), and promoted the phosphorylation of BAD. IRS-4 also promoted the activation of PKB/Akt and BAD phosphorylation during insulin stimulation; however, it weakly bound or activated p85-associated PI 3-kinase and failed to mediate the activation of p70(s6k). Insulin strongly inhibited apoptosis of interleukin-3 (IL-3)-deprived 32D(IR) cells expressing IRS-1 or IRS-2 but failed to inhibit apoptosis of cells expressing IRS-4. Consequently, 32D(IR) cells expressing IRS-4 proliferated slowly during insulin stimulation. Thus, the activation of PKB/Akt and BAD phosphorylation might not be sufficient to inhibit the apoptosis of IL-3-deprived 32D(IR) cells unless p85-associated PI 3-kinase or p70(s6k) are strongly activated.

Document information provided by NCBI PubMed

Text Mining Data

protein kinase B → IRS-4: " IRS-4 mediates protein kinase B signaling during insulin stimulation without promoting antiapoptosis "

mitogen activated protein kinase → insulin: " Insulin promoted the association of Grb-2 with IRS-1 and IRS-4, whereas IRS-2 weakly bound Grb-2 ; consequently, IRS-1 and IRS-4 enhanced insulin stimulated mitogen activated protein kinase activity "

Grb-2 → mitogen activated protein kinase: " Insulin promoted the association of Grb-2 with IRS-1 and IRS-4, whereas IRS-2 weakly bound Grb-2 ; consequently, IRS-1 and IRS-4 enhanced insulin stimulated mitogen activated protein kinase activity "

Grb-2 → Insulin: " Insulin promoted the association of Grb-2 with IRS-1 and IRS-4, whereas IRS-2 weakly bound Grb-2 ; consequently, IRS-1 and IRS-4 enhanced insulin stimulated mitogen activated protein kinase activity "

IRS-1 → mitogen activated protein kinase: " Insulin promoted the association of Grb-2 with IRS-1 and IRS-4, whereas IRS-2 weakly bound Grb-2 ; consequently, IRS-1 and IRS-4 enhanced insulin stimulated mitogen activated protein kinase activity "

IRS-1 → Insulin: " Insulin promoted the association of Grb-2 with IRS-1 and IRS-4, whereas IRS-2 weakly bound Grb-2 ; consequently, IRS-1 and IRS-4 enhanced insulin stimulated mitogen activated protein kinase activity "

IRS-4 → mitogen activated protein kinase: " Insulin promoted the association of Grb-2 with IRS-1 and IRS-4 , whereas IRS-2 weakly bound Grb-2 ; consequently, IRS-1 and IRS-4 enhanced insulin stimulated mitogen activated protein kinase activity "

IRS-4 → Insulin: " Insulin promoted the association of Grb-2 with IRS-1 and IRS-4 , whereas IRS-2 weakly bound Grb-2 ; consequently, IRS-1 and IRS-4 enhanced insulin stimulated mitogen activated protein kinase activity "

PKB/Akt → IRS-4: " IRS-4 also promoted the activation of PKB/Akt and BAD phosphorylation during insulin stimulation ; however, it weakly bound or activated p85 associated PI 3-kinase and failed to mediate the activation of p70 ( s6k ) "

PKB/Akt → PI 3-kinase: " IRS-4 also promoted the activation of PKB/Akt and BAD phosphorylation during insulin stimulation ; however, it weakly bound or activated p85 associated PI 3-kinase and failed to mediate the activation of p70 ( s6k ) "

PKB/Akt → IRS-4: " IRS-4 also promoted the activation of PKB/Akt and BAD phosphorylation during insulin stimulation ; however, it weakly bound or activated p85 associated PI 3-kinase and failed to mediate the activation of p70 ( s6k ) "

PKB/Akt → PI 3-kinase: " IRS-4 also promoted the activation of PKB/Akt and BAD phosphorylation during insulin stimulation ; however, it weakly bound or activated p85 associated PI 3-kinase and failed to mediate the activation of p70 ( s6k ) "

BAD → IRS-4: " IRS-4 also promoted the activation of PKB/Akt and BAD phosphorylation during insulin stimulation ; however, it weakly bound or activated p85 associated PI 3-kinase and failed to mediate the activation of p70 ( s6k ) "

BAD → PI 3-kinase: " IRS-4 also promoted the activation of PKB/Akt and BAD phosphorylation during insulin stimulation ; however, it weakly bound or activated p85 associated PI 3-kinase and failed to mediate the activation of p70 ( s6k ) "

Manually curated Databases

No curated data.