A Systems-Level Interrogation Identifies Regulators of Blood Cell Number and Survival

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Signaling networks that drive cell survival and proliferation regulate cell number in development and disease. We use a simple Drosophila model of cell number control, which centers on PDGF/VEGF receptor signaling. Performing a genome-wide RNAi screen under Pvr-sensitized conditions, we identify regulators of cell number that have not been found in conventional screens. Validation by in vivo genetics reveals previously unrecognized roles for EcR and InR in the balance of cell survival in the Drosophila embryo. Phosphoproteomic analysis demonstrates distinct mechanisms of cell survival regulation by EcR and receptor tyrosine kinase signaling. It further identifies common phosphorylation targets of Pvr and InR including regulators of cell survival, and receptor-specific phosphorylation targets mediating unique functions of Pvr and InR. Importantly, the study provides precedence that the selection of phosphorylation targets by signaling receptors can change with the signaling status of the cell, which may have wide-reaching implications for other cell regulatory systems.

Vyšlo v časopise: A Systems-Level Interrogation Identifies Regulators of Blood Cell Number and Survival. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005056
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005056

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