Format

Send to

Choose Destination
See comment in PubMed Commons below
Cell Metab. 2012 Jun 6;15(6):813-26. doi: 10.1016/j.cmet.2012.04.023.

The sedoheptulose kinase CARKL directs macrophage polarization through control of glucose metabolism.

Author information

  • 1Department of Laboratory Medicine, Medical University of Vienna, A-1090, Austria. arvand.haschemi@meduniwien.ac.at

Abstract

Immune cells are somewhat unique in that activation responses can alter quantitative phenotypes upwards of 100,000-fold. To date little is known about the metabolic adaptations necessary to mount such dramatic phenotypic shifts. Screening for novel regulators of macrophage activation, we found nonprotein kinases of glucose metabolism among the most enriched classes of candidate immune modulators. We find that one of these, the carbohydrate kinase-like protein CARKL, is rapidly downregulated in vitro and in vivo upon LPS stimulation in both mice and humans. Interestingly, CARKL catalyzes an orphan reaction in the pentose phosphate pathway, refocusing cellular metabolism to a high-redox state upon physiological or artificial downregulation. We find that CARKL-dependent metabolic reprogramming is required for proper M1- and M2-like macrophage polarization and uncover a rate-limiting requirement for appropriate glucose flux in macrophage polarization.

PMID:
22682222
PMCID:
PMC3370649
DOI:
10.1016/j.cmet.2012.04.023
[PubMed - indexed for MEDLINE]
Free PMC Article

Publication Types, MeSH Terms, Substances, Grant Support

Publication Types

MeSH Terms

Substances

Grant Support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center