PXD008824

PXD008824 is an original dataset announced via ProteomeXchange.

Title	Identification of non-overlapping functions between adaptor proteins NCK1 and NCK2
Description	Signals from cell surface receptors are often relayed via adaptor proteins. NCK1 and NCK2 are Src-Homology (SH) 2 and 3 domain adaptors that regulate processes requiring a remodelling of the actin cytoskeleton. Evidence from gene inactivation in mouse suggest that NCK1 and NCK2 are functionally redundant, although recent reports support the idea of unique functions for NCK1 and NCK2. We sought to examine this question further by delineating NCK1- and NCK2-specific signalling networks. We used both affinity purification-mass spectrometry and BioID proximity labelling to identify NCK1/2 signalling networks comprised of 98 proteins. Strikingly, we found 30 proteins restricted to NCK1 and 28 proteins specifically associated with NCK2, thus suggesting differences in their function. We report that Nck2-/-, but not Nck1-/- mouse embryo fibroblasts (MEFs) are multi-nucleated and display extended protrusions reminiscent of intercellular bridges, which correlate with an extended time spent in cytokinesis as well as a failure of a significant proportion of cells to complete abscission. Our data also show that the midbody of NCK2-deficient cells is not only increased in length, but also altered in composition, as judged by the mislocalization of AURKB, PLK1 and ECT2. Finally, we show that NCK2 function during cytokinesis requires its SH2 domain. Taken together, our data delineate the first high-confidence interactome for NCK1/2 adaptors and highlight a number of proteins specifically associated with either protein. We further demonstrate that contrary to what is generally accepted, NCK1 and NCK2 are not completely redundant, and shed light on a previously uncharacterized function for the NCK2 adaptor protein in cell division.
HostingRepository	PRIDE
AnnounceDate	2018-09-20
AnnouncementXML	Submission_2018-09-20_08:11:51.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kevin Jacquet
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	TripleTOF 5600; LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2018-01-31 03:35:25	ID requested
⏵ 1	2018-09-20 08:11:52	announced

Jacquet K, Banerjee SL, Chartier FJM, Elowe S, Bisson N, Proteomic Analysis of NCK1/2 Adaptors Uncovers Paralog-specific Interactions That Reveal a New Role for NCK2 in Cell Abscission During Cytokinesis. Mol Cell Proteomics, 17(10):1979-1990(2018) [pubmed]

curator keyword: Biological

submitter keyword: Mass spectrometry, Specificity, NCK adaptors

Nicolas Bisson
contact affiliation	Centre de Recherche sur le Cancer, PROTEO et Département de Biologie Moléculaire, Biochimie Médicale et Pathologie, Université Laval, Division Oncologie, Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Québec, Québec, Canada
contact email	Nick.Bisson@crchudequebec.ulaval.ca
lab head
Kevin Jacquet
contact affiliation	CRC quebec
contact email	kevin.jacquet.labobisson@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/09/PXD008824

PRIDE project URI

• PRIDE
  1. PXD008824
     1. Label: PRIDE project
     2. Name: Identification of non-overlapping functions between adaptor proteins NCK1 and NCK2