title: Early estrogen-induced gene 1, a novel RANK signaling component, is essential for osteoclastogenesis.
abstract: The receptor activator of NF-κB (RANK) and immunoreceptor tyrosine-based activation motif (ITAM)-containing adaptors are essential factors involved in regulating osteoclast formation and bone remodeling. Here, we identify early estrogen-induced gene 1 (EEIG1) as a novel RANK ligand (RANKL)-inducible protein that physically interacts with RANK and further associates with Gab2, PLCγ2 and Tec/Btk kinases upon RANKL stimulation. EEIG1 positively regulates RANKL-induced osteoclast formation, likely due to its ability to facilitate RANKL-stimulated PLCγ2 phosphorylation and NFATc1 induction. In addition, an inhibitory peptide designed to block RANK-EEIG1 interaction inhibited RANKL-induced bone destruction by reducing osteoclast formation. Together, our results identify EEIG1 as a novel RANK signaling component controlling RANK-mediated osteoclast formation, and suggest that targeting EEIG1 might represent a new therapeutic strategy for the treatment of pathological bone resorption.
authors.affiliation: Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Han Kyoung
authors.initials: HK
authors.lastname: Choi
authors.forename: Hye Ri
authors.initials: HR
authors.lastname: Kang
authors.forename: Eutteum
authors.initials: E
authors.lastname: Jung
authors.forename: Tae Eon
authors.initials: TE
authors.lastname: Kim
authors.forename: Jing Jing
authors.initials: JJ
authors.lastname: Lin
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Lee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001862:Bone Resorption / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051379:Mice; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D051966:Phospholipase C gamma / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011506:Proteins; D053245:RANK Ligand / Q000235:genetics* / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D050778:NFATC Transcription Factors; D010455:Peptides; D051966:Phospholipase C gamma; D011505:Protein-Tyrosine Kinases; D011506:Proteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C583401:EEIG1 protein, human; C490895:GAB2 protein, human; C494003:NFATC1 protein, human; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; C089848:Tec protein-tyrosine kinase