| First Author | Eliopoulos AG | Year | 2006 |
| Journal | J Biol Chem | Volume | 281 |
| Issue | 3 | Pages | 1371-80 |
| PubMed ID | 16291755 | Mgi Jnum | J:116388 |
| Mgi Id | MGI:3694174 | Doi | 10.1074/jbc.M506790200 |
| Citation | Eliopoulos AG, et al. (2006) The tyrosine kinase Syk regulates TPL2 activation signals. J Biol Chem 281(3):1371-80 |
| abstractText | Tpl2/Cot is a serine/threonine kinase that plays a key physiological role in the regulation of immune responses to pro-inflammatory stimuli, including tumor necrosis factor-alpha (TNF-alpha). TNF-alpha stimulates the JNK, ERK, and p38 mitogen-activated protein kinases and the NF-kappaB pathway by recruiting RIP1 and TRAF2 to the TNF receptor 1. Here we showed that Tpl2 activation by TNF-alpha signals depends on the integrity of the Tpl2-interacting proteins RIP1 and TRAF2, which are required for the engagement of the ERK mitogen-activated protein kinase pathway. However, neither RIP1 nor TRAF2 overexpression was sufficient to activate Tpl2 and ERK. We also showed that Tpl2 activation by TNF-alpha depends on a tyrosine kinase activity that is detected in TNF-alpha-stimulated cells. Based on both genetic and biochemical evidence, we concluded that in a variety of cell types, Syk is the tyrosine kinase that plays an important role in the activation of Tpl2 upstream of ERK. These data therefore dissect the TNF receptor 1 proximal events that regulate Tpl2 and ERK and highlight a role for RIP1, TRAF2, and Syk in this pathway. |
