PXD022084-1

PXD022084 is an original dataset announced via ProteomeXchange.

Title	FER-mediated phosphorylation and PIK3R2 recruitment on IRS4 promotes AKT activation and tumorigenesis in ovarian cancer
Description	Tyrosine phosphorylation, orchestrated by tyrosine kinases and phosphatases, modulates a multi-layered signaling network in a time and space dependent manner. Dysregulation of this post-translational modification is inevitably associated with pathological diseases. Our previous work has demonstrated that non-receptor tyrosine kinase FER is upregulated in ovarian cancer, knocking down of which attenuates metastatic phenotypes. Here we employed mass spectrometry and biochemical approaches to identify insulin receptor substrate 4 (IRS4) as a novel substrate of FER. Using a proximity-based tagging system, we determined that FER-mediated phosphorylation of Tyr779 enables IRS4 to recruit PIK3R2/p85β, the regulatory subunit of PI3K, and activate the PI3K-AKT pathway. Rescuing IRS4-null ovarian tumor cells with phosphorylation-defective mutant, but not WT IRS4, delayed tumor cell proliferation both in vitro and in vivo. Overall, we revealed a kinase-substrate mode between FER and IRS4, and the pharmacological inhibition of FER kinase may be beneficial for ovarian cancer patients with PI3K-AKT hyperactivation
HostingRepository	iProX
AnnounceDate	2020-10-19
AnnouncementXML	Submission_2020-10-19_20:53:29.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yanchun Zhang
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-19 20:51:26	ID requested
⏵ 1	2020-10-19 20:53:29	announced
2	2023-02-20 19:24:10	announced	2023-02-21: Update information.

Dataset with its publication pending

submitter keyword: Tyrosine phosphorylation

Gaofeng Fan
contact affiliation	ShanghaiTech University
contact email	fangf@shanghaitech.edu.cn
lab head
Yanchun Zhang
contact affiliation	ShanghaiTech University
contact email	zhangych3@shanghaitech.edu.cn
dataset submitter

iProX dataset URI