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Previous work demonstrates that phosphorylation of MITF by p38 MAPK downstream of Receptor Activator of NF<jats:sc>k<\/jats:sc>B Ligand (RANKL) signaling is necessary for MITF activation in osteoclasts. The spontaneous <jats:italic>Mitf cloudy eyed<\/jats:italic> (<jats:italic>ce<\/jats:italic>) allele results in production of a truncated MITF protein that lacks the leucine zipper and C\u2010terminal end. Here we show that the <jats:italic>Mitf<jats:sup>ce<\/jats:sup><\/jats:italic> allele leads to a dense bone phenotype in neonatal mice due to defective osteoclast differentiation. In response to RANKL stimulation, in vitro osteoclast differentiation was impaired in myeloid precursors derived from neonatal or adult <jats:italic>Mitf<jats:sup>ce\/ce<\/jats:sup><\/jats:italic> mice. The loss of the leucine zipper domain in <jats:italic>Mitf<jats:sup>ce\/ce<\/jats:sup><\/jats:italic> mice does not interfere with the recruitment of MITF\/PU.1 complexes to target promoters. Further, we have mapped the p38 MAPK docking site within the region deleted in <jats:italic>Mitf<jats:sup>ce<\/jats:sup><\/jats:italic>. This interaction is necessary for the phosphorylation of MITF by p38 MAPK. Site\u2010directed mutations in the docking site interfered with the interaction between MITF and its co\u2010factors FUS and BRG1. MITF\u2010ce fails to recruit FUS and BRG1 to target genes, resulting in decreased expression of target genes and impaired osteoclast function. These results highlight the crucial role of signaling dependent MITF\/p38 MAPK interactions in osteoclast differentiation. J. Cell. Physiol. 231: 630\u2013640, 2016. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.25108","type":"journal-article","created":{"date-parts":[[2015,7,27]],"date-time":"2015-07-27T10:58:27Z","timestamp":1437994707000},"page":"630-640","source":"Crossref","is-referenced-by-count":7,"title":["Failure to Target RANKL Signaling Through p38\u2010MAPK Results in Defective Osteoclastogenesis in the Microphthalmia Cloudy\u2010Eyed Mutant"],"prefix":"10.1002","volume":"231","author":[{"given":"Heather A.","family":"Carey","sequence":"first","affiliation":[{"name":"Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center The Ohio State University Wexner Medical Center Columbus Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"Bronisz","sequence":"additional","affiliation":[{"name":"Harvey Cushing Neuro\u2010Oncology Laboratories Department of Neurosurgery Brigham and Women's Hospital Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Cabrera","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center The Ohio State University Wexner Medical Center Columbus Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"III","given":"Blake E.","family":"Hildreth","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center The Ohio State University Wexner Medical Center Columbus Ohio"},{"name":"College of Veterinary Medicine The Ohio State University Columbus Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Cuiti\u00f1o","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center The Ohio State University Wexner Medical Center Columbus Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center The Ohio State University Wexner Medical Center Columbus Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asrar","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center The Ohio State University Wexner Medical Center Columbus Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramiro E.","family":"Toribio","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine The Ohio State University Columbus Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael C.","family":"Ostrowski","sequence":"additional","affiliation":[{"name":"Department of 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