| First Author | Hug E | Year | 2014 |
| Journal | Oncogene | Volume | 33 |
| Issue | 28 | Pages | 3730-41 |
| PubMed ID | 23955076 | Mgi Jnum | J:208904 |
| Mgi Id | MGI:5565221 | Doi | 10.1038/onc.2013.326 |
| Citation | Hug E, et al. (2014) Inducible expression of hyperactive Syk in B cells activates Blimp-1-dependent terminal differentiation. Oncogene 33(28):3730-41 |
| abstractText | The non-receptor protein tyrosine kinase Syk (spleen tyrosine kinase) is an important mediator of signal transduction in B cells. By acting downstream of the B-cell antigen receptor, Syk promotes signaling pathways involved in proliferation, differentiation and survival of B cells. To study the oncogenic potential of Syk, we generated a mouse model for the inducible expression of the leukemia-derived TEL-Syk fusion protein exhibiting constitutive kinase activity. To achieve B-cell-specific expression of TEL-Syk in adult mice, we used a tamoxifen-inducible Cre mouse line. This study shows that inducible expression of TEL-Syk in B cells leads to transient proliferation and subsequent plasma cell differentiation. However, it does not lead to B-cell transformation. Instead, Syk activation induces the tumor suppressor B-lymphocyte-induced maturation protein-1 (Blimp-1), which interferes with the expression of the antiapoptotic protein Bcl-2. Combined induction of TEL-Syk with transgenic expression of Bcl-2 results in a severe phenotype and plasma cell expansion. Our results suggest that deregulated Syk activity by itself is not sufficient for the transformation of B cells, as downstream effectors, such as Blimp-1, limit the survival and expansion of the activated B cell. |
