| First Author | Shinohara H | Year | 2014 |
| Journal | Science | Volume | 344 |
| Issue | 6185 | Pages | 760-4 |
| PubMed ID | 24833394 | Mgi Jnum | J:211255 |
| Mgi Id | MGI:5574369 | Doi | 10.1126/science.1250020 |
| Citation | Shinohara H, et al. (2014) Positive feedback within a kinase signaling complex functions as a switch mechanism for NF-kappaB activation. Science 344(6185):760-4 |
| abstractText | A switchlike response in nuclear factor-kappaB (NF-kappaB) activity implies the existence of a threshold in the NF-kappaB signaling module. We show that the CARD-containing MAGUK protein 1 (CARMA1, also called CARD11)-TAK1 (MAP3K7)-inhibitor of NF-kappaB (IkappaB) kinase-beta (IKKbeta) module is a switch mechanism for NF-kappaB activation in B cell receptor (BCR) signaling. Experimental and mathematical modeling analyses showed that IKK activity is regulated by positive feedback from IKKbeta to TAK1, generating a steep dose response to BCR stimulation. Mutation of the scaffolding protein CARMA1 at serine-578, an IKKbeta target, abrogated not only late TAK1 activity, but also the switchlike activation of NF-kappaB in single cells, suggesting that phosphorylation of this residue accounts for the feedback. |
