STAC2 negatively regulates osteoclast formation by targeting the RANK signaling complex
- 주제(기타) Biochemistry & Molecular Biology; Cell Biology
- 설명문(일반) [Jeong, Eutteum; Choi, Han Kyoung; Park, Jin Hee; Lee, Soo Young] Ewha Womans Univ, Dept Life Sci, Seoul 03760, South Korea; [Jeong, Eutteum; Choi, Han Kyoung; Park, Jin Hee; Lee, Soo Young] Ewha Womans Univ, Res Ctr Cellular Homeostasis, Seoul 03760, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 NATURE PUBLISHING GROUP
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000155851
- 본문언어 영어
- Published As http://dx.doi.org/10.1038/s41418-017-0048-5
초록/요약
The receptor activator of nuclear factor-kappa B (RANK) protein activates various protein kinase signaling cascades, including those involving NF-kappa B, mitogen-activated protein kinase (MAPK), and Bruton tyrosine kinase (Btk)/tyrosine-protein kinase Tec. However, the mechanism underlying the negative regulation of RANK by downstream signaling molecules remains unclear. Here, we report that Src homology 3 domain and cysteine-rich domain-containing protein 2 (STAC2) is a novel RANK ligand-inducible protein that negatively regulates RANK-mediated osteoclast formation. STAC2 physically interacts with RANK and inhibits the formation of the RANK signaling complex, which contains Grb-2-associated binder 2 (Gab2) and phospholipase C gamma 2 (PLC gamma 2), thus leading to the suppression of RANK-mediated NF-kappa B and MAPK activation. Furthermore, STAC2 overexpression limits Btk/Tec-mediated PLC gamma 2 phosphorylation via the interaction between STAC2 and Btk/Tec. Taken together, our results reveal a novel mechanism whereby RANK signaling is restricted by its physical interaction with STAC2.
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