Endothelial cells decode VEGF-mediated Ca2+ signaling patterns to produce distinct functional responses

dc.citation.articleNumberra20en_US
dc.citation.issueNumber416en_US
dc.citation.journalTitleScience Signalingen_US
dc.citation.volumeNumber9en_US
dc.contributor.authorNoren, David P.en_US
dc.contributor.authorChou, Wesley H.en_US
dc.contributor.authorLee, Sung Hoonen_US
dc.contributor.authorQutub, Amina A.en_US
dc.contributor.authorWarmflash, Aryehen_US
dc.contributor.authorWagner, Daniel S.en_US
dc.contributor.authorPopel, Aleksander S.en_US
dc.contributor.authorLevchenko, Andreen_US
dc.date.accessioned2017-05-24T16:33:35Zen_US
dc.date.available2017-05-24T16:33:35Zen_US
dc.date.issued2016en_US
dc.description.abstractA single extracellular stimulus can promote diverse behaviors among isogenic cells by differentially regulated signaling networks. We examined Ca2+ signaling in response to VEGF (vascular endothelial growth factor), a growth factor that can stimulate different behaviors in endothelial cells. We found that altering the amount of VEGF signaling in endothelial cells by stimulating them with different VEGF concentrations triggered distinct and mutually exclusive dynamic Ca2+ signaling responses that correlated with different cellular behaviors. These behaviors were cell proliferation involving the transcription factor NFAT (nuclear factor of activated T cells) and cell migration involving MLCK (myosin light chain kinase). Further analysis suggested that this signal decoding was robust to the noisy nature of the signal input. Using probabilistic modeling, we captured both the stochastic and deterministic aspects of Ca2+ signal decoding and accurately predicted cell responses in VEGF gradients, which we used to simulate different amounts of VEGF signaling. Ca2+ signaling patterns associated with proliferation and migration were detected during angiogenesis in developing zebrafish.en_US
dc.identifier.citationNoren, David P., Chou, Wesley H., Lee, Sung Hoon, et al.. "Endothelial cells decode VEGF-mediated Ca2+ signaling patterns to produce distinct functional responses." <i>Science Signaling,</i> 9, no. 416 (2016) American Association for the Advancement of Science: https://doi.org/10.1126/scisignal.aad3188.en_US
dc.identifier.doihttps://doi.org/10.1126/scisignal.aad3188en_US
dc.identifier.urihttps://hdl.handle.net/1911/94373en_US
dc.language.isoengen_US
dc.publisherAmerican Association for the Advancement of Scienceen_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by AAAS.en_US
dc.titleEndothelial cells decode VEGF-mediated Ca2+ signaling patterns to produce distinct functional responsesen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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