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• W2101844105 endingPage "424" @default.
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• W2101844105 abstract "ABSTRACT Current understanding of the activation of STATs is through binding between the SH2 domain of STATs and phosphotyrosine of tyrosine kinases. Here we demonstrate a novel role of RACK1 as an adaptor for insulin and insulin-like growth factor 1 receptor (IGF-1R)-mediated STAT3 activation specifically. Intracellular association of RACK1 via its N-terminal WD domains 1 to 4 (WD1-4) with insulin receptor (IR)/IGF-1R is augmented upon respective ligand stimulation, whereas association with STAT3 is constitutive. Purified RACK1 or RACK1 WD1-4 associates directly with purified IR, IGF-1R, and STAT3 in vitro. Insulin induces multiprotein complex formation of RACK1, IR, and STAT3. Overexpression or downregulation of RACK1 greatly enhances or decreases, respectively, IR/IGF-1R-mediated activation of STAT3 and its target gene expression. Site-specific mutants of IR and IGF-1R impaired in RACK1 binding are ineffective in mediating recruitment and activation of STAT3 as well as in insulin- or IGF-1-induced protection of cells from anoikis. RACK1-mediated STAT3 activation is important for insulin and IGF-1-induced anchorage-independent growth in certain ovarian cancer cells. We conclude that RACK1 mediates recruitment of STAT3 to IR and IGF-1R specifically for activation, suggesting a general paradigm for the need of an adaptor in mediating activation of STATs by receptor protein tyrosine kinases." @default.
• W2101844105 created "2016-06-24" @default.
• W2101844105 creator A5020997600 @default.
• W2101844105 creator A5026512599 @default.
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• W2101844105 creator A5039289448 @default.
• W2101844105 creator A5041054598 @default.
• W2101844105 creator A5090366670 @default.
• W2101844105 date "2006-01-15" @default.
• W2101844105 modified "2023-10-18" @default.
• W2101844105 title "RACK1 Recruits STAT3 Specifically to Insulin and Insulin-Like Growth Factor 1 Receptors for Activation, Which Is Important for Regulating Anchorage-Independent Growth" @default.
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• W2101844105 doi "https://doi.org/10.1128/mcb.26.2.413-424.2006" @default.
• W2101844105 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1346890" @default.
• W2101844105 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16382134" @default.
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