| First Author | Nandi S | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 30 | Pages | 21972-86 |
| PubMed ID | 23744080 | Mgi Jnum | J:202720 |
| Mgi Id | MGI:5521266 | Doi | 10.1074/jbc.M112.442731 |
| Citation | Nandi S, et al. (2013) Receptor-type protein-tyrosine phosphatase zeta is a functional receptor for interleukin-34. J Biol Chem 288(30):21972-86 |
| abstractText | Interleukin-34 (IL-34) is highly expressed in brain. IL-34 signaling via its cognate receptor, colony-stimulating factor-1 receptor (CSF-1R), is required for the development of microglia. However, the differential expression of IL-34 and the CSF-1R in brain suggests that IL-34 may signal via an alternate receptor. By IL-34 affinity chromatography of solubilized mouse brain membrane followed by mass spectrometric analysis, we identified receptor-type protein-tyrosine phosphatase zeta (PTP-zeta), a cell surface chondroitin sulfate (CS) proteoglycan, as a novel IL-34 receptor. PTP-zeta is primarily expressed on neural progenitors and glial cells and is highly expressed in human glioblastomas. IL-34 selectively bound PTP-zeta in CSF-1R-deficient U251 human glioblastoma cell lysates and inhibited the proliferation, clonogenicity, and motility of U251 cells in a PTP-zeta-dependent manner. These effects were correlated with an increase in tyrosine phosphorylation of the previously identified PTP-zeta downstream effectors focal adhesion kinase and paxillin. IL-34 binding to U251 cells was abrogated by chondroitinase ABC treatment, and CS competed with IL-34 for binding to the extracellular domain of PTP-zeta and to the cells, indicating a dependence of binding on PTP-zeta CS moieties. This study identifies an alternate receptor for IL-34 that may mediate its action on novel cellular targets. |
