PXD011061

PXD011061 is an original dataset announced via ProteomeXchange.

Title	Bi-directional signaling by membrane-bound KitL induces proliferation and co-ordinates thymic endothelial cell and thymocyte expansion
Description	The ligand for the c-Kit receptor, KitL, exists as a membrane-associated (mKitL) and a soluble form (sKitL). KitL functions outside c-Kit activation have not been identified. We show that co-culture of c-Kit– and mKitL–expressing NIH3T3 cells results in signaling through mKitL: c-Kit–bound mKitL recruits calcium-modulating cyclophilin ligand (CAML) to selectively activate Akt, leading to CREB phosphorylation, mTOR pathway activation, and increased cell proliferation. Activation of mKitL in thymic vascular endothelial cells (VECs) induces mKitL- and Akt-dependent proliferation, and genetic ablation of mKitL in thymic VECs blocks their c-Kit responsiveness and proliferation during neonatal thymic expansion. Therefore, mKitL–c-Kit form a bi-directional signaling complex that acts in the developing thymus to coordinate thymic VEC and early thymic progenitor (ETP) expansion by simultaneously promoting ETP survival and VEC proliferation. This mechanism may be relevant to both normal tissues and malignant tumors that depend on KitL–c-Kit signaling for their proliferation.
HostingRepository	PRIDE
AnnounceDate	2018-11-21
AnnouncementXML	Submission_2019-04-03_04:29:26.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Roman Fischer
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2018-09-11 06:48:56	ID requested
1	2018-11-21 05:20:01	announced
⏵ 2	2019-04-03 04:29:28	announced	Updated publication reference for PubMed record(s): 30410062.

Buono M, Th, é, z, é, nas ML, Ceroni A, Fischer R, Nerlov C, Bi-directional signaling by membrane-bound KitL induces proliferation and coordinates thymic endothelial cell and thymocyte expansion. Nat Commun, 9(1):4685(2018) [pubmed]

submitter keyword: Kit ligand, thymocyte expansion, bi-directional signalling

Roman Fischer
contact affiliation	Discovery Proteomics Facility
contact email	roman.fischer@ndm.ox.ac.uk
lab head
Roman Fischer
contact affiliation	University of Oxford
contact email	roman.fischer@ndm.ox.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD011061
     1. Label: PRIDE project
     2. Name: Bi-directional signaling by membrane-bound KitL induces proliferation and co-ordinates thymic endothelial cell and thymocyte expansion