| First Author | Beer S | Year | 2005 |
| Journal | Mol Cell Biol | Volume | 25 |
| Issue | 21 | Pages | 9646-60 |
| PubMed ID | 16227612 | Mgi Jnum | J:102171 |
| Mgi Id | MGI:3607020 | Doi | 10.1128/MCB.25.21.9646-9660.2005 |
| Citation | Beer S, et al. (2005) Impaired immune responses and prolonged allograft survival in Sly1 mutant mice. Mol Cell Biol 25(21):9646-60 |
| abstractText | Adaptive immunity is crucial for protective host defense and the development of immunological disorders. SLY1 was recently identified as an X-chromosomal SH3 protein that is serine phosphorylated (Ser27) upon B-and T-cell receptor engagement. Here, we demonstrate that SLY1 is localized in the cytoplasm and the nucleus of immunocytes. We generated mice expressing a mutant version of SLY1 lacking Ser27 and a functional nuclear localization signal. The defective SLY1 (SLY1(d)) protein is localized exclusively in the cytoplasm. B- and T-cell proliferation is attenuated and T-cell cytokine production is severely reduced. Sly1(d/d) mice exhibit reduced lymphoid organ sizes, diminished marginal zone B-cell numbers, and severely impaired antibody responses against T-dependent and -independent antigens. Importantly, survival of semi-identical cardiac allografts was substantially prolonged in Sly1(d/d) mice. These results define SLY1 as an essential molecular component for the full activation of adaptive immunity. |
