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dc.contributor.authorKwak, E.-A.
dc.contributor.authorPan, C.C.
dc.contributor.authorRamonett, A.
dc.contributor.authorKumar, S.
dc.contributor.authorCruz-Flores, P.
dc.contributor.authorAhmed, T.
dc.contributor.authorOrtiz, H.R.
dc.contributor.authorLochhead, J.J.
dc.contributor.authorEllis, N.A.
dc.contributor.authorMouneimne, G.
dc.contributor.authorGeorgieva, T.G.
dc.contributor.authorLee, Y.S.
dc.contributor.authorVanderah, T.W.
dc.contributor.authorLargent-Milnes, T.
dc.contributor.authorMohler, P.J.
dc.contributor.authorHund, T.J.
dc.contributor.authorLanglais, P.R.
dc.contributor.authorMythreye, K.
dc.contributor.authorLee, N.Y.
dc.identifier.citationKwak, E.-A., Pan, C. C., Ramonett, A., Kumar, S., Cruz-Flores, P., Ahmed, T., Ortiz, H. R., Lochhead, J. J., Ellis, N. A., Mouneimne, G., Georgieva, T. G., Lee, Y. S., Vanderah, T. W., Largent-Milnes, T., Mohler, P. J., Hund, T. J., Langlais, P. R., Mythreye, K., & Lee, N. Y. (2022). ΒIV-spectrin as a stalk cell-intrinsic regulator of VEGF signaling. Nature Communications.
dc.description.abstractDefective angiogenesis underlies over 50 malignant, ischemic and inflammatory disorders yet long-term therapeutic applications inevitably fail, thus highlighting the need for greater understanding of the vast crosstalk and compensatory mechanisms. Based on proteomic profiling of angiogenic endothelial components, here we report βIV-spectrin, a non-erythrocytic cytoskeletal protein, as a critical regulator of sprouting angiogenesis. Early loss of endothelial-specific βIV-spectrin promotes embryonic lethality in mice due to hypervascularization and hemorrhagic defects whereas neonatal depletion yields higher vascular density and tip cell populations in developing retina. During sprouting, βIV-spectrin expresses in stalk cells to inhibit their tip cell potential by enhancing VEGFR2 turnover in a manner independent of most cell-fate determining mechanisms. Rather, βIV-spectrin recruits CaMKII to the plasma membrane to directly phosphorylate VEGFR2 at Ser984, a previously undefined phosphoregulatory site that strongly induces VEGFR2 internalization and degradation. These findings support a distinct spectrin-based mechanism of tip-stalk cell specification during vascular development. © 2022, The Author(s).
dc.publisherNature Research
dc.rightsCopyright © The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License.
dc.titleβIV-spectrin as a stalk cell-intrinsic regulator of VEGF signaling
dc.contributor.departmentDepartment of Pharmacology, University of Arizona
dc.contributor.departmentDepartment of Chemistry & Biochemistry, University of Arizona
dc.contributor.departmentBIO5 Institute, University of Arizona
dc.contributor.departmentDepartment of Internal Medicine, University of Arizona
dc.contributor.departmentCancer Center, University of Arizona
dc.identifier.journalNature Communications
dc.description.noteOpen access journal
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at
dc.eprint.versionFinal published version
dc.source.journaltitleNature Communications

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Copyright © The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License.
Except where otherwise noted, this item's license is described as Copyright © The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License.