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• W2090171844 endingPage "9814" @default.
• W2090171844 startingPage "9810" @default.
• W2090171844 abstract "While Ras activation has been shown to play an important role in signal transduction by the T-lymphocyte antigen receptor, the mechanism of its activation in T cells is unclear. Membrane localization of the guanine nucleotide exchange factor Sos, but not Vav or Dbl, was sufficient for Ras-mediated signaling in T lymphocytes. Activation of Sos appears to involve membrane recruitment and not allosteric changes, because interaction of Sos with the linking molecule Grb-2 was not required for Ras activation. To extend this analysis, we constructed a modified Sos that could be localized to the membrane inducibly by using a rationally designed chemical inducer of dimerization, FK1012. The role of Grb-2 in signaling was mimicked with this technique, which induced the association of a modified Sos with the membrane, resulting in rapid activation of Ras-induced signaling. In contrast, inducible localization of Grb-2 to the membrane did not activate signaling and suggests that the interaction of Grb-2 with Sos in T cells is subject to regulation. This conditional allele of Sos demonstrates that membrane localization of Sos is sufficient for Ras activation in T cells and indicates that the role of Grb-2 is to realize the biologic advantages of linker-mediated dimerization: enhanced specificity and favorable kinetics for signaling. This method of generating conditional alleles may also be useful in dissecting other signal transduction pathways regulated by protein localization or protein-protein interactions." @default.
• W2090171844 created "2016-06-24" @default.
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• W2090171844 date "1995-10-10" @default.
• W2090171844 modified "2023-10-18" @default.
• W2090171844 title "Signal transduction in T lymphocytes using a conditional allele of Sos." @default.
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• W2090171844 doi "https://doi.org/10.1073/pnas.92.21.9810" @default.
• W2090171844 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/40892" @default.
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