PXD054302 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Development of a Peptide Inhibitor Targeting the C-SH2 Domain of the SHP2 Phosphatase |
Description | Src homology 2 (SH2) domain-containing phosphatase 2 (SHP2) has important cellular functions in mediating signal transduction downstream of receptor tyrosine kinases and immune cell receptors. In T cells, SHP2 is a key regulator of signalling pathways downstream of the checkpoint receptor programmed cell death protein 1 (PD-1) that suppresses T cell activation, and of the T cell receptor (TCR) that promotes T cell activation. SHP2 contains two SH2 domains: the N-SH2 and C-SH2 domains. Here, we describe a new approach for the chemical targeting of SHP2 by developing a peptide inhibitor, containing a non-hydrolysable phosphotyrosine (pTyr) mimetic, which selectively binds to the C-SH2 domain of SHP2. We found that incorporation of the pTyr mimetic L-O-malonyltyrosine (L-OMT) displayed robust binding affinity to the C-SH2 domain, while the widely used pTyr mimetic phosphonodifluoromethyl phenylalanine (F2Pmp) abolished binding, showing that the use of pTyr mimetics for SH2 domains is case dependent. Our C-SH2 inhibitor peptide (CSIP) impedes SHP2 activation and inhibits SHP2 phosphatase activity in vitro. CSIP is stable, cell permeable and non-cytotoxic in a model T cell line (Jurkat), in which it displays cellular activity in modulating T cell activation. As such, CSIP is a powerful chemical tool to study SHP2, in particular the role of its C-SH2 domain, in cellular contexts. CSIP enriches the toolbox of inhibitors with different modes of action to study SHP2. |
HostingRepository | PRIDE |
AnnounceDate | 2025-05-09 |
AnnouncementXML | Submission_2025-05-09_06:59:08.278.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Julian Bender |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | acetylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive Plus |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-07-28 00:49:06 | ID requested | |
⏵ 1 | 2025-05-09 06:59:08 | announced | |
Publication List
Keyword List
submitter keyword: pulldown,SHP2, inhibitor, chemical biology, C-SH2 Domain |
Contact List
Bettina Warscheid |
contact affiliation | Chair of Biochemistry II, Theodor Boveri-Institute, Biocenter, University of Würzburg, Würzburg, Germany |
contact email | bettina.warscheid@uni-wuerzburg.de |
lab head | |
Julian Bender |
contact affiliation | University of Wuerzburg
Chair of Biochemistry II
Am Hubland
97074 Würzburg |
contact email | julian.bender@uni-wuerzburg.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD054302
- Label: PRIDE project
- Name: Development of a Peptide Inhibitor Targeting the C-SH2 Domain of the SHP2 Phosphatase