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Multiplex matrix network analysis of protein complexes in the human TCR signalosome

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Science Signaling  02 Aug 2016:
Vol. 9, Issue 439, pp. rs7
DOI: 10.1126/scisignal.aad7279

Personalized signaling complexes

The response of a cell to ligands that activate cell surface receptors depends on the resulting protein-protein interactions that occur. The formation of different protein complexes leads to the activation of different intracellular signaling pathways and different cellular outputs. Thus, knowing which protein-protein interactions occur can be clinically important. To analyze these complexes in patient samples, Smith et al. devised a multiplex, antibody-based method and used it to capture complexes from T cell lysates and identify binding partners by flow cytometry. Mathematical analyses of these data enabled the construction of protein-protein interaction networks and revealed the relative abundances of particular complexes between resting and stimulated cells. Application of this technique to T cells from skin biopsies identified protein complexes that differed in their relative abundance between control donors and patients with an autoimmune skin disease. This type of analysis brings basic research a step closer to personalized therapy and may be useful as a diagnostic tool.

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