title: The transmembrane adaptor protein, linker for activation of T cells (LAT), regulates RANKL-induced osteoclast differentiation.
abstract: RANKL induces the formation of osteoclasts, which are responsible for bone resorption. Herein we investigate the role of the transmembrane adaptor proteins in RANKL-induced osteoclastogenesis. LAT positively regulates osteoclast differentiation and is up-regulated by RANKL via c-Fos and NFATc1, whereas LAB and LIME act as negative modulators of osteoclastogenesis. In addition, silencing of LAT by RNA interference or overexpression of a LAT dominant negative in bone marrow-derived macrophage cells attenuates RANKL-induced osteoclast formation. Furthermore, LAT is involved in RANKL-induced PLC(γ) activation and NFATc1 induction. Thus, our data suggest that LAT acts as a positive regulator of RANKL-induced osteoclastogenesis.
authors.affiliation: National Research Laboratory for Regulation of Bone Metabolism and Disease, Department of Pharmacology, Chonnam National University Medical School, Gwangju 501-746, Korea. kabsun@hanmail.net
authors.forename: Kabsun
authors.initials: K
authors.lastname: Kim
authors.forename: Jung Ha
authors.initials: JH
authors.lastname: Kim
authors.forename: Jang Bae
authors.initials: JB
authors.lastname: Moon
authors.forename: Jongwon
authors.initials: J
authors.lastname: Lee
authors.forename: Han Bok
authors.initials: HB
authors.lastname: Kwak
authors.forename: Yong-Wook
authors.initials: YW
authors.lastname: Park
authors.forename: Nacksung
authors.initials: N
authors.lastname: Kim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D051966:Phospholipase C gamma / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000172:deficiency / Q000235:genetics; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C491734:Lat protein, mouse; D008565:Membrane Proteins; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D010750:Phosphoproteins; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D051966:Phospholipase C gamma