PXD023687

PXD023687 is an original dataset announced via ProteomeXchange.

Title	Characterization of PEAK3 pseudokinase as a pro-migratory and -invasive member of New Kinase Family 3
Description	The New Kinase Family 3 (NKF3) of pseudokinases comprises PEAK1 and PEAK2 as well as the recently-identified PEAK3. PEAK1/2 play fundamental roles in regulating tyrosine kinase signal output and oncogenesis, while PEAK3 remains poorly-characterized. Here we demonstrate that PEAK3 undergoes homotypic association as well as heterotypic interaction with PEAK1/2. PEAK3 also recruits ASAP1/2, Grb2, CrkII, Cbl and PYK2 with effector recruitment being dependent on PEAK3 dimerization. PEAK3 tyrosine phosphorylation on Y24 is also dependent on dimerization as well as Src family kinase activity, and interestingly, is decreased via PTPN12 in response to EGF treatment. Both phosphorylation of Y24 and an intact N-terminal SH3 binding motif are required for optimal binding of Grb2, CrkII and ASAP1. Overexpression of PEAK3 in MDA-MB-231 breast cancer cells enhanced cell elongation and cell motility, while knockdown of endogenous PEAK3 decreased cell migration. In addition, overexpression of PEAK3 in PEAK1/2 compound knock-out MCF-10A breast epithelial cells enhanced acinar growth and invasion in 3D culture, with the latter phenotype dependent on PEAK3 tyrosine phosphorylation and ASAP1 binding. These findings characterize PEAK3 as an integral member of NKF3 with scaffolding roles that promote cell proliferation, migration and invasion.
HostingRepository	PRIDE
AnnounceDate	2022-03-14
AnnouncementXML	Submission_2022-03-16_03:09:41.788.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hugh Ma
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2021-01-19 22:39:47	ID requested
1	2022-03-14 08:14:58	announced
⏵ 2	2022-03-16 03:09:42	announced	2022-03-16: Updated publication reference for PubMed record(s): 35192416.

Hou J, Nguyen EV, Surudoi M, Roy MJ, Patel O, Lucet IS, Ma X, Daly RJ, Distinct PEAK3 interactors and outputs expand the signaling potential of the PEAK pseudokinase family. Sci Signal, 15(722):eabj3554(2022) [pubmed]

ProteomeXchange project tag: Human Proteome Project

submitter keyword: NKF3/ PEAK1 (SgK269)/ PEAK2 (SgK223, Pragmin)/ PEAK3/Brest cancer

Roger John Daly
contact affiliation	Monash Biomedicine Discovery Institute Department of Biochemistry and Molecular Biology Monash University
contact email	roger.daly@monash.edu
lab head
Hugh Ma
contact affiliation	Monash University
contact email	hugh.ma@monash.edu
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/2022/03/PXD023687

PRIDE project URI

• PRIDE
  1. PXD023687
     1. Label: PRIDE project
     2. Name: Characterization of PEAK3 pseudokinase as a pro-migratory and -invasive member of New Kinase Family 3