| First Author | Leonoudakis D | Year | 2010 |
| Journal | J Cell Sci | Volume | 123 |
| Issue | Pt 21 | Pages | 3683-92 |
| PubMed ID | 20940259 | Mgi Jnum | J:182923 |
| Mgi Id | MGI:5317086 | Doi | 10.1242/jcs.070680 |
| Citation | Leonoudakis D, et al. (2010) Dystroglycan controls signaling of multiple hormones through modulation of STAT5 activity. J Cell Sci 123(Pt 21):3683-92 |
| abstractText | Receptors for basement membrane (BM) proteins, including dystroglycan (DG), coordinate tissue development and function by mechanisms that are only partially defined. To further elucidate these mechanisms, we generated a conditional knockout of DG in the epithelial compartment of the mouse mammary gland. Deletion of DG caused an inhibition of mammary epithelial outgrowth and a failure of lactation. Surprisingly, loss of DG in vivo did not disrupt normal tissue architecture or BM formation, even though cultured Dag1-null epithelial cells failed to assemble laminin-111 at the cell surface. The absence of DG was, however, associated with a marked loss in activity of signal transducer and activator of transcription 5 (STAT5). Loss of DG perturbed STAT5 signaling induced by either prolactin or growth hormone. We found that DG regulates signaling by both hormones in a manner that is dependent on laminin-111 binding, but independent of the DG cytoplasmic domain, suggesting that it acts via a co-receptor mechanism reliant on DG-mediated laminin assembly. These results demonstrate a requirement for DG in the growth and function of a mammalian epithelial tissue in vivo. Moreover, we reveal a selective role for DG in the control of multiple STAT5-dependent hormone signaling pathways, with implications for numerous diseases in which DG function is compromised. |
