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PXD022084

PXD022084 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleFER-mediated phosphorylation and PIK3R2 recruitment on IRS4 promotes AKT activation and tumorigenesis in ovarian cancer
DescriptionTyrosine 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
HostingRepositoryiProX
AnnounceDate2020-10-19
AnnouncementXMLSubmission_2023-02-20_19:24:09.486.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterYanchun Zhang
SpeciesList scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationListphosphorylated residue
InstrumentTripleTOF 5600
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-10-19 20:51:26ID requested
12020-10-19 20:53:29announced
22023-02-20 19:24:10announced2023-02-21: Update information.
Publication List
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]
Keyword List
submitter keyword: Tyrosine phosphorylation
Contact List
Gaofeng Fan
contact affiliationShanghaiTech University
contact emailfangf@shanghaitech.edu.cn
lab head
Yanchun Zhang
contact affiliationShanghaiTech University
contact emailzhangych3@shanghaitech.edu.cn
dataset submitter
Full Dataset Link List
iProX dataset URI