GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:12189148

From GONUTS
Jump to: navigation, search
Citation

Shalom-Barak, T and Knaus, UG (2002) A p21-activated kinase-controlled metabolic switch up-regulates phagocyte NADPH oxidase. J. Biol. Chem. 277:40659-65

Abstract

Chemoattractant-stimulated phagocytes increase their glucose uptake and divert energy production from glycolysis to the pentose phosphate pathway to generate NADPH. NADPH is a required cofactor for the NADPH oxidase to produce reactive oxygen metabolites, an important microbicidal tool in host defense. p21-Activated kinases (Paks) are regulated by the GTPases Rac and Cdc42 and control actin dynamics and phosphorylation of the oxidase component p47(phox). Here we report the interaction of Pak with phosphoglycerate mutase (PGAM)-B, an enzyme of the glycolytic pathway. Activated Pak1 inhibits glycolysis by association of its catalytic domain with PGAM-B and subsequent phosphorylation of the enzyme on serine residues 23 and 118, thereby abolishing PGAM activity. Leukocyte activation through chemoattractant receptors leads to Pak activation and transient inhibition of endogenous PGAM-B activity. Consistent with these observations, treatment of neutrophils with phosphoglycolic acid, a competitive PGAM-B inhibitor, increases upstream intermediates, thereby amplifying the respiratory burst. These results demonstrate that Rho GTPases regulate the glycolytic pathway through Pak and suggest a link between chemoattractant signaling and metabolic responses to enhance host defense.

Links

PubMed Online version:10.1074/jbc.M206650200

Keywords

Humans; NADPH Oxidase/metabolism; Phagocytes/enzymology; Phosphoglycerate Mutase/antagonists & inhibitors; Phosphoglycerate Mutase/metabolism; Protein-Serine-Threonine Kinases/metabolism; Substrate Specificity; Up-Regulation

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:PGAM1

enables

GO:0019901: protein kinase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13153

F

Seeded From UniProt

complete

HUMAN:PGAM1

located_in

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PGAM1

involved_in

GO:0006110: regulation of glycolytic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PGAM1

enables

GO:0004619: phosphoglycerate mutase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:PGAM1

involved_in

GO:0045730: respiratory burst

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PGAM1

involved_in

GO:0043456: regulation of pentose-phosphate shunt

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PAK1

enables

GO:0005518: collagen binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P18669

F

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.