Research Article

Cell-Specific Information Processing in Segregating Populations of Eph Receptor Ephrin–Expressing Cells

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Science  11 Dec 2009:
Vol. 326, Issue 5959, pp. 1502-1509
DOI: 10.1126/science.1176615

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Cells have self-organizing properties that control their behavior in complex tissues. Contact between cells expressing either B-type Eph receptors or their transmembrane ephrin ligands initiates bidirectional signals that regulate cell positioning. However, simultaneously investigating how information is processed in two interacting cell types remains a challenge. We implemented a proteomic strategy to systematically determine cell-specific signaling networks underlying EphB2- and ephrin-B1–controlled cell sorting. Quantitative mass spectrometric analysis of mixed populations of EphB2- and ephrin-B1–expressing cells that were labeled with different isotopes revealed cell-specific tyrosine phosphorylation events. Functional associations between these phosphotyrosine signaling networks and cell sorting were established with small interfering RNA screening. Data-driven network modeling revealed that signaling between mixed EphB2- and ephrin-B1–expressing cells is asymmetric and that the distinct cell types use different tyrosine kinases and targets to process signals induced by cell-cell contact. We provide systems- and cell-specific network models of contact-initiated signaling between two distinct cell types.

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