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PXD030006-1

PXD030006 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleRegulation of Src tumor activity by its N-terminal intrinsically disordered region
DescriptionThe membrane anchored Src tyrosine kinase is involved in numerous pathways and its deregulation is involved in human cancer. Our knowledge on Src regulation relies on crystallography, which revealed intramolecular interactions to control active Src conformations. However, Src contains a N-terminal intrinsically disordered unique domain (UD) whose function remains unclear. Using NMR, we reported that UD forms an intramolecular fuzzy complex involving a conserved region with lipid-binding capacity named Unique Lipid Binding Region (ULBR), which could modulate Src membrane anchoring. Here we show that the ULBR is essential for Src’s oncogenic capacity. ULBR inactive mutations inhibited Src transforming activity in NIH3T3 cells and in human colon cancer cells. It also reduced Src-induced tumor development in nude mice. An intact ULBR was required for MAPK signaling without affecting Src kinase activity nor sub-cellular localization. Phospho-proteomic analyses revealed that, while not impacting on the global tyrosine phospho-proteome in colon cancer cells, this region modulates phosphorylation of specific membrane-localized tyrosine kinases needed for Src oncogenic signaling, including EPHA2 and Fyn. Collectively, this study reveals an important role of this intrinsically disordered region in malignant cell transformation and suggests a novel layer of Src regulation by this unique region via membrane substrate phosphorylation.
HostingRepositoryPRIDE
AnnounceDate2022-01-14
AnnouncementXMLSubmission_2022-01-14_08:21:47.727.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterRomain Hamelin
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-11-28 05:42:52ID requested
12022-01-14 08:21:48announced
22022-01-14 08:22:46announced2022-01-14: Updated publication reference for PubMed record(s): 34999732.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: cell signaling, intrinsically disordered region, protein kinase, cell transformation
Contact List
Serge ROCHE
contact affiliationCRBM, CNRS, Univ. Montpellier, F-34000, Montpellier France. Equipe labellisée Ligue Contre le Cancer, CRBM, CNRS, Univ. Montpellier, F-34000, Montpellier France.
contact emailserge.roche@crbm.cnrs.fr
lab head
Romain Hamelin
contact affiliationPCF
contact emailromain.hamelin@epfl.ch
dataset submitter
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