GCK is essential to systemic inflammation and pattern recognition receptor signaling to JNK and p38

Citation metadata

Publisher: National Academy of Sciences
Document Type: Author abstract; Clinical report
Length: 164 words

Document controls

Main content

Abstract :

Systemic inflammation arising from the organismal distribution of pathogen-associated molecular patterns is a major cause of clinical morbidity and mortality. Herein we report a critical and previously unrecognized in vivo role for germinal center kinase (GCK, genome nomenclature: map4k2), a mammalian Sterile 20 (STE20) orthologue, in PAMP signaling, and systemic inflammation. We find that disruption of gck in mice strongly impairs PAMP-stimulated macrophage cytokine and chemokine release and renders mice resistant to endotoxin-mediated lethality. Bone marrow transplantation studies show that hematopoietic cell GCK signaling is essential to systemic inflammation. Disruption of gck substantially reduces PAMP activation of macrophage Jun-N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (MAPKs) via reduced activation of the MAPK-kinase-kinases (MAP3Ks) mixed lineage kinases (MLKs)-2 and -3. Extracellular signal-regulated kinase (ERK) and nuclear factor-[kappa]B (NF-[kappa]B) activation are largely unaffected. Thus, GCK is an essential PAMP effector coupling JNK and p38, but not ERK or NF-[kappa]B to systemic inflammation. MAPK | sepsis | innate immunity | toll-like receptor | germinal center kinase

Source Citation

Source Citation   

Gale Document Number: GALE|A196962843