PXD009122

PXD009122 is an original dataset announced via ProteomeXchange.

Title	The BCKDH kinase and phosphatase integrate BCAA and lipid metabolism via regulation of ATP-citrate lyase
Description	Strong associations exist between branched chain amino acids (BCAA) and dysregulated glucose and lipid metabolism, but the underlying mechanisms are not well understood. Here we report that inhibition of the kinase (BDK) or overexpression of the phosphatase (PPM1K) that regulate branched-chain ketoacid dehydrogenase (BCKDH), the committed step of BCAA catabolism, lowers circulating BCAA, reduces hepatic steatosis and improves glucose tolerance in the absence of weight loss in Zucker fatty rats. Phosphoproteomics analysis identified ATP-citrate lyase (ACL) as an alternate substrate of BDK and PPM1K. Overexpression of BDK in liver of lean rats increased ACL phosphorylation and activated de novo lipogenesis. Moreover, BDK and PPM1K transcript levels were increased and repressed, respectively, in response to fructose feeding and expression of the ChREBP transcription factor. These studies identify BDK and PPM1K as a regulatory node that integrates BCAA, glucose, and lipid metabolism via reciprocal regulation of BCKDH and ACL. Modulation of this node relieves key disease phenotypes in a genetic model of severe obesity and metabolic dysfunction.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:43:36.123.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Paul Grimsrud
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-03-06 08:48:26	ID requested
1	2018-05-18 06:55:45	announced
2	2018-05-22 05:55:06	announced	Updated publication reference for PubMed record(s): 29779826.
⏵ 3	2024-10-22 04:43:44	announced	2024-10-22: Updated project metadata.

10.1016/j.cmet.2018.04.015;

White PJ, McGarrah RW, Grimsrud PA, Tso SC, Yang WH, Haldeman JM, Grenier-Larouche T, An J, Lapworth AL, Astapova I, Hannou SA, George T, Arlotto M, Olson LB, Lai M, Zhang GF, Ilkayeva O, Herman MA, Wynn RM, Chuang DT, Newgard CB, The BCKDH Kinase and Phosphatase Integrate BCAA and Lipid Metabolism via Regulation of ATP-Citrate Lyase. Cell Metab, 27(6):1281-1293.e7(2018) [pubmed]

curator keyword: Biological

submitter keyword: PPM1K, ACL, BDK, Protein Phosphorylation,BCAA

Christopher B. Newgard
contact affiliation	Director, Duke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Metabolism Center Professor Departments of Medicine (Division of Endocrinology, Metabolism, and Nutrition) and Pharmacology & Cancer Biology Duke University Medical Center
contact email	chris.newgard@duke.edu
lab head
Paul Grimsrud
contact affiliation	Duke Molecular Physiology Institute
contact email	paul.grimsrud@duke.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD009122
     1. Label: PRIDE project
     2. Name: The BCKDH kinase and phosphatase integrate BCAA and lipid metabolism via regulation of ATP-citrate lyase