PXD026618 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | βIV-spectrin as a stalk cell-intrinsic regulator of VEGF signaling |
Description | Defective 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. |
HostingRepository | PRIDE |
AnnounceDate | 2022-02-04 |
AnnouncementXML | Submission_2022-02-04_01:29:11.957.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD026618 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Paul Langlais |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | phosphorylated residue; acetylated residue; monohydroxylated residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-06-10 07:54:25 | ID requested | |
⏵ 1 | 2022-02-04 01:29:12 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Sprouting angiogenesis |
VEGF signaling |
tip-stalk cell specification |
spectrins |
Contact List
Nam Lee |
contact affiliation | University of Arizona College of Medicine-Tucson |
contact email | namlee@arizona.edu |
lab head | |
Paul Langlais |
contact affiliation | University of Arizona |
contact email | langlais@deptofmed.arizona.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD026618
- Label: PRIDE project
- Name: βIV-spectrin as a stalk cell-intrinsic regulator of VEGF signaling