| First Author | Naramura M | Year | 1998 |
| Journal | Proc Natl Acad Sci U S A | Volume | 95 |
| Issue | 26 | Pages | 15547-52 |
| PubMed ID | 9861006 | Mgi Jnum | J:51666 |
| Mgi Id | MGI:1321433 | Doi | 10.1073/pnas.95.26.15547 |
| Citation | Naramura M, et al. (1998) Altered thymic positive selection and intracellular signals in Cbl-deficient mice. Proc Natl Acad Sci U S A 95(26):15547-52 |
| abstractText | Cbl is the product of the protooncogene c-cbl and is involved in T cell antigen receptor (TCR)-mediated signaling. To understand the role of Cbl for immune system development and function, we generated a Cbl-deficient mouse strain. In Cbl-deficient mice, positive selection of the thymocytes expressing major histocompatibility complex class II-restricted transgenic TCR was significantly enhanced. Two factors may have contributed to the altered thymic selection. First, Cbl deficiency markedly up-regulated the activity of ZAP-70 and mitogen-activated protein kinases. The mitogen-activated protein kinase pathway was shown previously to be involved in thymic positive selection. Second, Cbl-deficient thymocytes expressed CD3 and CD4 molecules at higher levels, which consequently may increase the avidity of TCR/major histocompatibility complex/coreceptor interaction. Thus, Cbl plays a novel role in modulating TCR-mediated multiple signaling pathways and fine-tunes the signaling threshold for thymic selection. |
