| First Author | Tanaka S | Year | 1996 |
| Journal | Nature | Volume | 383 |
| Issue | 6600 | Pages | 528-31 |
| PubMed ID | 8849724 | Mgi Jnum | J:35825 |
| Mgi Id | MGI:83269 | Doi | 10.1038/383528a0 |
| Citation | Tanaka S, et al. (1996) c-Cbl is downstream of c-Src in a signalling pathway necessary for bone resorption. Nature 383(6600):528-31 |
| abstractText | The primary defect in mice lacking the c-src gene is osteopetrosis, a deficiency in bone resorption by osteoclasts. Osteoclasts express high levels of the c-Src protein and the defect responsible for the osteopetrotic phenotype of the c-src-deficient (src-) mouse is cell-autonomous and occurs in mature osteoclasts. However, the specific signalling pathways that require c-Src expression for normal osteoclast activity have not been elucidated. We report here that the proto-oncogene product c-Cbl is tyrosine-phosphorylated in a Src-dependent manner in osteoclasts, where the two proteins colocalize on some vesicular structures. In vitro bone resorption by osteoclast-like cells (OCLs) is inhibited by both c-src and c-cbl antisense oligonucleotides. Furthermore, tyrosine phosphorylation of c-Cbl and the localization of c-Cbl-containing structures to the peripheral cytoskeleton are impaired in resorption-deficient c-src- OCLs, as well as in wild-type OCLs that have been treated with c-src antisense oligonucleotides. These results indicate that c-Cbl may act downstream of c-Src in a signalling pathway that is required for bone resorption. |
