PXD049235-1

PXD049235 is an original dataset announced via ProteomeXchange.

Title	PKM2 functions as a histidine kinase to phosphorylate PGAM1 to increase glycolysis shunts in cancer
Description	Phosphoglycerate mutase 1 (PGAM1) is a key-node enzyme that diverts the metabolic intermediates from glycolysis into its shunts to support macromolecule biosynthesis for rapid and sustainable cell proliferation. It is prevalent that PGAM1 activity is upregulated in various tumors; however, the underlying mechanism remains unclear. Here, we unveil that pyruvate kinase M2 (PKM2) moonlights as a histidine kinase in a phosphoenolpyruvate (PEP)-dependent manner to catalyze PGAM1 H11 phosphorylation, that is essential for PGAM1 activity. Moreover, the dimeric or monomeric PKM2 in tumor cells phosphorylates PGAM1 more efficiently than the tetrameric one. In response to epidermal growth factor (EGF), Src signaling triggered PGAM1 Y119 phosphorylation is a prerequisite for PKM2 binding and the subsequent H11 phosphorylation of PGAM1, which constitutes the discrepancy between tumor cells and normal ones. A PGAM1-derived pY119-containing cell-permeable peptide or Y119 mutation disrupts the interaction of PGAM1 with PKM2 and its H11 phosphorylation, and eventually dampens the glycolysis shunts and tumor growth. We not only identifes a histidine kinase function of PKM2, but also illustrates an enzymes-cross-talk regulatory mode during metabolic reprogramming.
HostingRepository	PRIDE
AnnounceDate	2024-03-21
AnnouncementXML	Submission_2024-03-20_19:48:18.076.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Min Wei
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-07 03:28:35	ID requested
⏵ 1	2024-03-20 19:48:18	announced

Dataset with its publication pending

submitter keyword: glycolysis shunts, pyruvate kinase M2 (PKM2), histidine kinase, phosphorylation,phosphoglycerate mutase 1 (PGAM1)

Min Wei
contact affiliation	Northeast Normal University
contact email	weim750@nenu.edu.cn
lab head
Min Wei
contact affiliation	Key Laboratory of Molecular Epigenetics of the Ministry of Education (MOE), Northeast Normal University
contact email	weim750@nenu.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD049235
     1. Label: PRIDE project
     2. Name: PKM2 functions as a histidine kinase to phosphorylate PGAM1 to increase glycolysis shunts in cancer