PXD030006-2

PXD030006 is an original dataset announced via ProteomeXchange.

Title	Regulation of Src tumor activity by its N-terminal intrinsically disordered region
Description	The 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.
HostingRepository	PRIDE
AnnounceDate	2022-01-14
AnnouncementXML	Submission_2022-01-14_08:22:46.118.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Romain Hamelin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-28 05:42:52	ID requested
1	2022-01-14 08:21:48	announced
⏵ 2	2022-01-14 08:22:46	announced	2022-01-14: Updated publication reference for PubMed record(s): 34999732.

Aponte E, Lafitte M, Sirvent A, Simon V, Barbery M, Fourgous E, Boublik Y, Maffei M, Armand F, Hamelin R, Pannequin J, Fort P, Pons M, Roche S, Regulation of Src tumor activity by its N-terminal intrinsically disordered region. Oncogene, 41(7):960-970(2022) [pubmed]

submitter keyword: cell signaling, intrinsically disordered region, protein kinase, cell transformation

Serge ROCHE
contact affiliation	CRBM, CNRS, Univ. Montpellier, F-34000, Montpellier France. Equipe labellisée Ligue Contre le Cancer, CRBM, CNRS, Univ. Montpellier, F-34000, Montpellier France.
contact email	serge.roche@crbm.cnrs.fr
lab head
Romain Hamelin
contact affiliation	PCF
contact email	romain.hamelin@epfl.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD030006
     1. Label: PRIDE project
     2. Name: Regulation of Src tumor activity by its N-terminal intrinsically disordered region