{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T08:13:56Z","timestamp":1773303236469,"version":"3.50.1"},"reference-count":62,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2011,8,18]],"date-time":"2011-08-18T00:00:00Z","timestamp":1313625600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2011,8,18]],"date-time":"2011-08-18T00:00:00Z","timestamp":1313625600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2011,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The tyrosine kinase c\u2010Src and transcription factor NF\u2010\u03baB are considered crucial components required for normal osteoclastogenesis. Genetic ablation of either pathway leads to detrimental osteopetrotic phenotypes in mice. Similarly, obstruction of either pathway halts osteoclastogenesis and lessens various forms of bone loss. It has been shown previously that mice expressing a kinase domain\u2010truncated c\u2010Src, termed Src251, develop severe osteopetrosis owing to increased osteoclast apoptosis. It was further suggested that this phenomenon is associated with reduced Akt kinase activity. However, the precise mechanism underlying the osteoclast inhibitory effect of Src251 remains obscure. C\u2010Src associates with TRAF6\u2010p62 interacting with receptor activator of NF\u2010\u03baB (RANK) distal region and the complex facilitate activation of RANK down stream signal transduction cascades including NF\u2010\u03baB. Given this proximity between c\u2010Src and NF\u2010\u03baB signaling in osteoclasts, we surmised that inhibition of osteoclastogenesis by Src251 may be achieved through inhibition of NF\u2010\u03baB signaling. We have demonstrated recently that NEMO, the regulatory subunit of the IKK complex, is crucial for osteoclastogenesis and interacts with c\u2010Src in osteoclast progenitors. Transfection studies, in which we employed various forms of c\u2010Src and NEMO, revealed that the dominant negative form of c\u2010Src, namely Src251, mediates degradation of NEMO thus halting NF\u2010\u03baB signaling. Furthermore, degradation of NEMO requires its intact zinc finger domain which is located at the ubiquitination domain. This process also requires appropriate cellular localization of Src251, since deletion of its myristoylation domain ablates its degradation capacity. Buttressing these findings, the expression of NEMO and NF\u2010\u03baB signaling were significantly reduced in monocytes collected from Src251 transgenic mice. J. Cell. Biochem. 112: 2463\u20132470, 2011. \u00a9 2011 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.23170","type":"journal-article","created":{"date-parts":[[2011,5,2]],"date-time":"2011-05-02T07:57:48Z","timestamp":1304323068000},"page":"2463-2470","source":"Crossref","is-referenced-by-count":10,"title":["Evidence that the kinase\u2010truncated c\u2010Src regulates NF\u2010\u03baB signaling by targeting 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