| First Author | Choi SH | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 2 | Pages | e32378 |
| PubMed ID | 22384232 | Mgi Jnum | J:185297 |
| Mgi Id | MGI:5428081 | Doi | 10.1371/journal.pone.0032378 |
| Citation | Choi SH, et al. (2012) Spleen tyrosine kinase regulates AP-1 dependent transcriptional response to minimally oxidized LDL. PLoS One 7(2):e32378 |
| abstractText | Oxidative modification of low-density lipoprotein (LDL) turns it into an endogenous ligand recognized by pattern-recognition receptors. We have demonstrated that minimally oxidized LDL (mmLDL) binds to CD14 and mediates TLR4/MD-2-dependent responses in macrophages, many of which are MyD88-independent. We have also demonstrated that the mmLDL activation leads to recruitment of spleen tyrosine kinase (Syk) to TLR4 and TLR4 and Syk phosphorylation. In this study, we produced a macrophage-specific Syk knockout mouse and used primary Syk(-/-) macrophages in our studies. We demonstrated that Syk mediated phosphorylation of ERK1/2 and JNK, which in turn phosphorylated c-Fos and c-Jun, respectively, as assessed by an in vitro kinase assay. c-Jun phosphorylation was also mediated by IKKepsilon. c-Jun and c-Fos bound to consensus DNA sites and thereby completed an AP-1 transcriptional complex and induced expression of CXCL2 and IL-6. These results suggest that Syk plays a key role in TLR4-mediated macrophage responses to host-generated ligands, like mmLDL, with subsequent activation of an AP-1 transcription program. |
