| First Author | Qiao G | Year | 2008 |
| Journal | Mol Cell Biol | Volume | 28 |
| Issue | 7 | Pages | 2470-80 |
| PubMed ID | 18227156 | Mgi Jnum | J:134206 |
| Mgi Id | MGI:3785130 | Doi | 10.1128/MCB.01505-07 |
| Citation | Qiao G, et al. (2008) T-cell receptor-induced NF-kappaB activation is negatively regulated by E3 ubiquitin ligase Cbl-b. Mol Cell Biol 28(7):2470-80 |
| abstractText | It has previously been shown that E3 ubiquitin ligase Casitas B-lineage lymphoma-b (Cbl-b) negatively regulates T-cell activation, but the molecular mechanism(s) underlying this inhibition is not completely defined. In this study, we report that the loss of Cbl-b selectively results in aberrant activation of NF-kappaB upon T-cell antigen receptor (TCR) ligation, which is mediated by phosphatidylinositol 3-kinase (PI3-K)/Akt and protein kinase C-theta (PKC-theta). TCR-induced hyperactivation of Akt in the absence of Cbl-b may potentiate the formation of caspase recruitment domain-containing membrane-associated guanylate kinase protein 1 (CARMA1)-B-cell lymphoma/leukemia 10 (Bcl10)-mucosa-associated lymphatic tissue 1(MALT1) (CBM) complex, which appears to be independent of PKC-theta. Cbl-b associates with PKC-theta upon TCR stimulation and regulates TCR-induced PKC-theta activation via Vav-1, which couples PKC-theta to PI3-K and allows it to be phosphorylated. PKC-theta then couples IkappaB kinases (IKKs) to the CBM complex, resulting in the activation of the IKK complex. Therefore, our data provide the first evidence to demonstrate that the down-regulation of TCR-induced NF-kappaB activation by Cbl-b is mediated coordinately by both Akt-dependent and PKC-theta-dependent signaling pathways in primary T cells. |
