PXD052217

PXD052217 is an original dataset announced via ProteomeXchange.

Title	Parallel phosphoproteomics and metabolomics map the global metabolic tyrosine phosphoproteome
Description	Tyrosine phosphorylation of metabolic enzymes is an evolutionarily conserved post-translational modification that facilitates rapid and reversible modulation of enzyme activity, localization or function. Despite the high abundance of tyrosine phosphorylation events detected on metabolic enzymes in high-throughput mass spectrometry-based studies, functional characterization of tyrosine phosphorylation sites has been limited to a subset of enzymes. Since tyrosine phosphorylation is dysregulated across human diseases, including cancer, understanding the consequences of metabolic enzyme tyrosine phosphorylation events is critical for informing disease biology and therapeutic interventions. To globally identify metabolic enzyme tyrosine phosphorylation events and simultaneously assign functional significance to these sites, we performed parallel phosphoproteomics and polar metabolomics in non-tumorigenic mammary epithelial cells (MCF10A) stimulated with epidermal growth factor (EGF) in the absence or presence of the epidermal growth factor receptor (EGFR) inhibitor erlotinib. We performed an integrated analysis of the phosphoproteomic and metabolomic datasets to identify tyrosine phosphorylation sites on metabolic enzymes with functional consequences. We identified two previously characterized (PKM, PGAM1) and two novel (GSTP1, GLUD1) tyrosine phosphorylation sites on metabolic enzymes with purported functions based on metabolomic analyses. We validated these hits using a doxycycline-inducible CRISPR interference (CRISPRi) system in MCF10A cells, in which target metabolic enzymes were depleted with simultaneous re-expression of wild-type, phosphomutant or phosphomimetic isoforms. Together, these data provide a framework for identification, prioritization and characterization of tyrosine phosphorylation sites on metabolic enzymes with functional significance.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_09:34:04.177.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD052217
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Tigist Tamir
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Exploris 480; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-13 07:09:53	ID requested
⏵ 1	2025-05-06 09:34:04	announced

10.6019/PXD052217;

Hillis AL, Tamir T, Perry GE, Asara JM, Johnson JL, Yaron TM, Cantley LC, White FM, Toker A, Parallel phosphoproteomics and metabolomics map the global metabolic tyrosine phosphoproteome. Proc Natl Acad Sci U S A, 121(47):e2413837121(2024) [pubmed]

10.1073/pnas.2413837121;

submitter keyword: Metabolomics, EGF signaling, Phosphoprotoemics,Tyrosine Phosphorylation

Forest White
contact affiliation	Koch Institute for Integrative Cancer Research at MIT
contact email	fwhite@mit.edu
lab head
Tigist Tamir
contact affiliation	University of North Carolina at Chapel Hill, Department of Biochemistry and Biophysics
contact email	tytamir@mit.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD052217
     1. Label: PRIDE project
     2. Name: Parallel phosphoproteomics and metabolomics map the global metabolic tyrosine phosphoproteome