SHEP1 partners with CasL to promote marginal zone B-cell maturation
| Autor: | Yann Wallez, Derek V. Ostertag, Cecille D. Browne, Suresh K. Chintalapati, Robert C. Rickert, Elena B. Pasquale, Matthew H. Cato, Melanie M. Hoefer |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Mice
Knockout Scaffold protein B-Lymphocytes Multidisciplinary breakpoint cluster region Receptors Antigen B-Cell Signal transducing adaptor protein Biological Sciences Biology Marginal zone Cell biology Mice Receptors Lysosphingolipid Cell Movement Sphingosine Marginal zone B-cell Animals Lysophospholipids Phosphorylation Signal transduction Receptor Spleen Adaptor Proteins Signal Transducing Signal Transduction G protein-coupled receptor |
| Zdroj: | Proceedings of the National Academy of Sciences. 107:18944-18949 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1007558107 |
| Popis: | The marginal zone is a cellular niche bordering the marginal sinus of the spleen that contains specialized B-cell and macrophage subsets poised to capture bloodborne antigens. Marginal zone B cells are retained in this niche by integrin-mediated signaling induced by G protein-coupled receptors (GPCRs) and, likely, the B-cell receptor (BCR). Sphingosine-1-phosphate (S1P) signaling via the S1P family of GPCRs is known to be essential for B-cell localization in the marginal zone, but little is known about the downstream signaling events involved. Here, we demonstrate that the adaptor protein SHEP1 is required for marginal zone B-cell maturation. SHEP1 functions in concert with the scaffolding protein CasL, because we show that SHEP1 and CasL are constitutively associated in B cells. SHEP1 association is required for the BCR or S1P receptor(s) to induce the conversion of CasL into its serine/threonine hyperphosphorylated form, which is important for lymphocyte adhesion and motility. Thus, SHEP1 orchestrates marginal zone B-cell movement and retention as a key downstream effector of the BCR and S1P receptors. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|