PXD041786

PXD041786 is an original dataset announced via ProteomeXchange.

Title	Ubiquitin ligase and signalling hub MYCBP2 is required for efficient EPHB2 tyrosine kinase receptor function
Description	Eph receptor tyrosine kinases participate in a variety of normal and pathogenic processes during development and throughout adulthood. This versatility is likely facilitated by the ability of Eph receptors to signal through diverse cellular signalling pathways: primarily by controlling cytoskeletal dynamics, but also by regulating cellular growth, proliferation, and survival. Despite many proteins linked to these signalling pathways interacting with Eph receptors, the specific mechanisms behind such links and their coordination remain to be elucidated. In a proteomics screen for novel EPHB2 multi-effector proteins, we identified human MYC binding protein 2 (MYCBP2 or PAM or Phr1). MYCBP2 is a large signalling hub involved in diverse processes such as neuronal connectivity, synaptic growth, cell division, neuronal survival, and protein ubiquitination. Our biochemical experiments demonstrate that the formation of a complex containing EPHB2 and MYCBP2 is facilitated by FBXO45, a protein known to select substrates for MYCBP2 ubiquitin ligase activity. Formation of the MYCBP2-EPHB2 complex does not require EPHB2 tyrosine kinase activity and is destabilised by binding of ephrin-B ligands, suggesting that the MYCBP2-EPHB2 association is a prelude to EPHB2 signalling. Paradoxically, the loss of MYCBP2 results in increased ubiquitination of EPHB2 and a decrease of its protein levels suggesting that MYCBP2 stabilises EPHB2. Commensurate with this effect, our cellular experiments reveal that MYCBP2 is essential for efficient EPHB2 signalling responses in cell lines and primary neurons. Finally, our genetic studies in C. elegans provide in vivo evidence that the ephrin receptor VAB-1 displays genetic interactions with known MYCBP2 binding proteins. Together, our results align with the similarity of neurodevelopmental phenotypes caused by MYCBP2 and EPHB2 loss of function, and couple EPHB2 to a signalling effector that controls diverse cellular functions.
HostingRepository	PRIDE
AnnounceDate	2024-01-29
AnnouncementXML	Submission_2024-01-29_06:20:55.543.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD041786
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Sara Luiza Banerjee
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-24 13:08:23	ID requested
⏵ 1	2024-01-29 06:20:55	announced

10.6019/PXD041786;

submitter keyword: AP-MS,EPHB2, LC-MS/MS

Artur Kania
contact affiliation	Institut de recherches cliniques de Montréal (IRCM), Montréal, QC, H2W 1R7, Canada Integrated Program in Neuroscience, McGill University, Montréal, QC, H3A 2B4, Canada Division of Experimental Medicine, McGill University, Montréal, QC, H3A 2B2, Canada Department of Anatomy and Cell Biology, McGill University, Montréal, QC, H3A 0C7, Canada
contact email	artur.kania@ircm.qc.ca
lab head
Sara Luiza Banerjee
contact affiliation	Institut de recherches cliniques de Montréal - McGill University
contact email	banerjee.sara@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041786
     1. Label: PRIDE project
     2. Name: Ubiquitin ligase and signalling hub MYCBP2 is required for efficient EPHB2 tyrosine kinase receptor function