The Sedoheptulose Kinase CARKL Directs Macrophage Polarization through Control of Glucose Metabolism

详细信息	查看全文 | 推荐本文 |

• 作者：Arvand Haschemi¹ ; ⁶ ; ^{arvand.haschemi@meduniwien.ac.at} ; Paul Kosma⁷ ; Lars Gille⁸ ; Charles  ; R. Evans⁹ ; Charles  ; F. Burant⁹ ; Philipp Starkl² ; Bernhard Knapp³ ; Robert Haas¹ ; Johannes  ; A. Schmid⁴ ; Christoph Jandl¹ ; Shahzada Amir¹ ; Gert Lubec⁵ ; Jaehong Park¹⁰ ; ¹⁴ ; Harald Esterbauer¹ ; Martin Bilban¹ ; Leonardo Brizuela¹⁰ ; ¹³ ; J.  ; Andrew Pospisilik¹¹ ; ^{pospisilik@immunbio.mpg.de} ; Leo  ; E. Otterbein⁶ ; ¹² ; Oswald Wagner¹ ; ¹²
• 刊名：Cell Metabolism
• 出版年：2012
• 期刊代码：46_15504131
• 类别：med
• 出版时间：6 June, 2012
• 卷：15
• 期：6
• 页码：813-826
• 文件大小：2182 K

摘要

| Figures/TablesFigures/Tables | ReferencesReferences

Summary

Immune cells are somewhat unique in that activation聽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聽vitro and in聽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.