| First Author | Cohen S | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 1 | Pages | 259-69 |
| PubMed ID | 22140262 | Mgi Jnum | J:180892 |
| Mgi Id | MGI:5308140 | Doi | 10.4049/jimmunol.1101468 |
| Citation | Cohen S, et al. (2012) The cytokine midkine and its receptor RPTPzeta regulate B cell survival in a pathway induced by CD74. J Immunol 188(1):259-69 |
| abstractText | Lasting B cell persistence depends on survival signals that are transduced by cell surface receptors. In this study, we describe a novel biological mechanism essential for survival and homeostasis of normal peripheral mature B cells and chronic lymphocytic leukemia cells, regulated by the heparin-binding cytokine, midkine (MK), and its proteoglycan receptor, the receptor-type tyrosine phosphatase zeta (RPTPzeta). We demonstrate that MK initiates a signaling cascade leading to B cell survival by binding to RPTPzeta. In mice lacking PTPRZ, the proportion and number of the mature B cell population are reduced. Our results emphasize a unique and critical function for MK signaling in the previously described MIF/CD74-induced survival pathway. Stimulation of CD74 with MIF leads to c-Met activation, resulting in elevation of MK expression in both normal mouse splenic B and chronic lymphocytic leukemia cells. Our results indicate that MK and RPTPzeta are important regulators of the B cell repertoire. These findings could pave the way toward understanding the mechanisms shaping B cell survival and suggest novel therapeutic strategies based on the blockade of the MK/RPTPzeta-dependent survival pathway. |
