| First Author | Nie L | Year | 2008 |
| Journal | Mol Cell Biol | Volume | 28 |
| Issue | 6 | Pages | 2078-90 |
| PubMed ID | 18195039 | Mgi Jnum | J:132669 |
| Mgi Id | MGI:3776622 | Doi | 10.1128/MCB.00844-07 |
| Citation | Nie L, et al. (2008) Regulation of lymphocyte development by cell-type-specific interpretation of notch signals. Mol Cell Biol 28(6):2078-90 |
| abstractText | Notch signaling pathways exert diverse biological effects depending on the cellular context where Notch receptors are activated. How Notch signaling is integrated with environmental cues is a central issue. Here, we show that Notch activation accelerates ubiquitin-mediated and mitogen-activated protein kinase (MAPK)-dependent degradation of E2A transcription factors and Janus kinases, molecules essential for both B- and T-lymphocyte development. However, these events occur in B lymphocytes, but not T lymphocytes, due to their different levels of MAPK, thus providing one mechanism whereby Notch inhibits B-cell development without impairing T-cell differentiation. Lymphoid progenitors expressing a Notch-resistant E2A mutant differentiated into B-lineage cells on stromal cells expressing Notch ligands and in the thymus of transplant recipients. Bone marrow transplant assays and examination of steady-state B lymphopoiesis also revealed that the expression of Notch-resistant E2A and constitutively active STAT5 in mice neutralized the effects of Notch-induced degradation, allowing B-cell development through a bone marrow-like program in the thymus. These findings illustrate that Notch function can be influenced by MAPKs, producing distinct outcomes in different cellular contexts. |
