| First Author | Sun J | Year | 2008 |
| Journal | Proc Natl Acad Sci U S A | Volume | 105 |
| Issue | 44 | Pages | 17085-90 |
| PubMed ID | 18952848 | Mgi Jnum | J:248230 |
| Mgi Id | MGI:6092781 | Doi | 10.1073/pnas.0802701105 |
| Citation | Sun J, et al. (2008) Beta-arrestin 2 is required for lysophosphatidic acid-induced NF-kappaB activation. Proc Natl Acad Sci U S A 105(44):17085-90 |
| abstractText | Lysophosphatidic acid (LPA) is a bioactive phospholipid and binds to its receptors, a family of G protein-coupled receptors (GPCR), which initiates multiple signaling cascades and leads to activation of several transcription factors, including NF-kappaB. Although LPA-induced signaling pathways have been intensively investigated, the molecular mechanism by which LPA activates NF-kappaB is not fully defined. In this work, we found that beta-arrestin 2, but not beta-arrestin 1, is required for LPA-induced NF-kappaB activation and interlukin-6 expression. Mechanistically, we found that beta-arrestin 2 associated with CARMA3, a scaffold protein that plays an essential role in GPCR-induced NF-kappaB activation, suggesting that beta-arrestin 2 may recruit CARMA3 to LPA receptors. Although beta-arrestin 2 deficiency did not affect LPA-induced IKKalpha/beta phosphorylation, it impaired LPA-induced IKK kinase activity, which is consistent with our previous findings that CARMA3 is required for IKKalpha/beta activation but not for the inducible phosphorylation of IKKalpha/beta. Together, our results provide the genetic evidence that beta-arrestin 2 serves as a positive regulator in NF-kappaB signaling pathway by connecting CARMA3 to GPCRs. |
