PXD049310

PXD049310 is an original dataset announced via ProteomeXchange.

Title	PKM2 functions as a histidine kinase to phosphorylate PGAM1 to increase glycolysis shunts in cancer-Cellular lipid level assessment
Description	Phosphoglycerate mutase 1 (PGAM1) is a key node enzyme that diverts the metabolic reactions 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, monomeric and dimeric PKM2 are efficient to phosphorylate and activate PGAM1, while the tetrameric PKM2 is not. In response to epidermal growth factor (EGF) signaling, Src-catalyzed PGAM1 Y119 phosphorylation is a prerequisite for PKM2 binding and the subsequent PGAM1 H11 phosphorylation, which constitutes the discrepancy between tumor cells and normal ones. A PGAM1-derived pY119-containing cell-permeable peptide or Y119 mutation disrupted the interaction of PGAM1 with PKM2 and its H11 phosphorylation, and eventually dampened the glycolysis shunts and tumor growth. We not only identified a function of PKM2 as a histidine kinase, but also illustrated an enzymes-cross-talk regulatory mode during metabolic reprogramming.
HostingRepository	PRIDE
AnnounceDate	2024-03-21
AnnouncementXML	Submission_2024-03-20_19:48:55.205.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	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-09 17:58:00	ID requested
⏵ 1	2024-03-20 19:48:55	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. PXD049310
     1. Label: PRIDE project
     2. Name: PKM2 functions as a histidine kinase to phosphorylate PGAM1 to increase glycolysis shunts in cancer-Cellular lipid level assessment