| First Author | Zhong J | Year | 2009 |
| Journal | Proc Natl Acad Sci U S A | Volume | 106 |
| Issue | 11 | Pages | 4372-7 |
| PubMed ID | 19246396 | Mgi Jnum | J:146772 |
| Mgi Id | MGI:3838430 | Doi | 10.1073/pnas.0812642106 |
| Citation | Zhong J, et al. (2009) GCK is essential to systemic inflammation and pattern recognition receptor signaling to JNK and p38. (RETRACTED Proc Natl Acad Sci U S A. 2012 Mar 27;109(13):5134). Proc Natl Acad Sci U S A 106(11):4372-7 |
| abstractText | 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-kappaB (NF-kappaB) activation are largely unaffected. Thus, GCK is an essential PAMP effector coupling JNK and p38, but not ERK or NF-kappaB to systemic inflammation. |
