PXD028404

PXD028404 is an original dataset announced via ProteomeXchange.

Title	Systematic Identification of SHP2 Phosphatase Substrates
Description	Phosphatases play essential roles in normal cell physiology and diseases like cancer. The challenges of studying phosphatases have limited our understanding of their substrates, molecular mechanisms, and unique functions within highly complicate networks. Here we introduce a novel strategy using substrate trapping mutant coupled with quantitative mass spectrometry to identify physiological substrates of protein tyrosine phosphatase Src homology 2 containing protein tyrosine phosphatase 2 (SHP2) in a high-throughput manner. SHP2 plays a critical role in numerous cellular processes through the regulation of various signaling pathways. The method integrates three separate MS-based experiments; in vitro dephosphorylation assay, in vivo global phosphoproteomics, and pull down of substrate trapping mutant complex using HEK293SHP2KO cells. PTPN11-C459S/D425A is an optimized substrate trap mutant of SHP2. We identified eleven direct substrates, including both known and novel SHP2 substrates in EGFR signaling pathways, among which docking protein 1 (DOK1) was further validated as a new SHP2 substrate. This advanced workflow significantly improves the systemic identification of direct substrates of phosphatase, facilitating the comprehension of equally important roles of phosphatase signaling.
HostingRepository	PRIDE
AnnounceDate	2022-09-20
AnnouncementXML	Submission_2022-09-20_07:57:08.520.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD028404
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Peipei Zhu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-09 09:00:44	ID requested
⏵ 1	2022-09-20 07:57:09	announced

Zhu P, Wu X, Zhang RY, Hsu CC, Zhang ZY, Tao WA, An Integrated Proteomic Strategy to Identify SHP2 Substrates. J Proteome Res, 21(10):2515-2525(2022) [pubmed]

ProteomeXchange project tag: Human Proteome Project

submitter keyword: Phosphoproteomics, SHP2, LC-MS, tyrosine phosphatase substrates

Weiguo Andy Tao
contact affiliation	Department of Biochemistry, Department of Chemistry, Purdue University, West Lafayette, IN 47906
contact email	taow@purdue.edu
lab head
Peipei Zhu
contact affiliation	Purdue University
contact email	zhu517@purdue.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD028404
     1. Label: PRIDE project
     2. Name: Systematic Identification of SHP2 Phosphatase Substrates