PXD022084-2

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_2023-02-20_19:24:09.486.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.

Zhang Y, Xiong X, Zhu Q, Zhang J, Chen S, Wang Y, Cao J, Chen L, Hou L, Zhao X, Hao P, Chen J, Zhuang M, Li D, Fan G, FER-mediated phosphorylation and PIK3R2 recruitment on IRS4 promotes AKT activation and tumorigenesis in ovarian cancer cells. Elife, 11():(2022) [pubmed]

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