| First Author | Jaeschke A | Year | 2007 |
| Journal | Mol Cell | Volume | 27 |
| Issue | 3 | Pages | 498-508 |
| PubMed ID | 17679097 | Mgi Jnum | J:134814 |
| Mgi Id | MGI:3789833 | Doi | 10.1016/j.molcel.2007.07.008 |
| Citation | Jaeschke A, et al. (2007) Metabolic stress signaling mediated by mixed-lineage kinases. Mol Cell 27(3):498-508 |
| abstractText | Saturated free fatty acid (FFA) is a major source of metabolic stress that activates the c-Jun NH(2)-terminal kinase (JNK). This FFA-stimulated JNK pathway is relevant to hallmarks of metabolic syndrome, including insulin resistance. Here we used gene ablation studies in mice to demonstrate a central role for mixed-lineage protein kinases (MLK) in this signaling pathway. Saturated FFA causes protein kinase C (PKC)-dependent activation of MLK3 that subsequently causes increased JNK activity by a mechanism that requires the MAP kinase kinases MKK4 and MKK7. Loss of PKC, MLK3, MKK4, or MKK7 expression prevents FFA-stimulated JNK activation. Together, these data establish a signaling pathway that mediates effects of metabolic stress on insulin resistance. |
