RACK1 interaction with c-Src is essential for osteoclast function

Jin Hee Park, Eutteum Jeong, Jingjing Lin, Ryeojin Ko, Ji Hee Kim, Sol Yi, Youngjin Choi, In Cheol Kang, Daekee Lee, Soo Young Lee

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

The scaffolding protein receptor for activated C-kinase 1 (RACK1) mediates receptor activator of nuclear factor κΒ ligand (RANKL)-dependent activation of p38 MAPK in osteoclast precursors; however, the role of RACK1 in mature osteoclasts is unclear. The aim of our study was to identify the interaction between RACK1 and c-Src that is critical for osteoclast function. A RACK1 mutant protein (mutations of tyrosine 228 and 246 residues to phenylalanine; RACK1 Y228F/Y246F) did not interact with c-Src. The mutant retained its ability to differentiate into osteoclasts; however, the integrity of the RANKL-mediated cytoskeleton, bone resorption activity, and phosphorylation of c-Src was significantly decreased. Importantly, lysine 152 (K152) within the Src homology 2 (SH2) domain of c-Src is involved in RACK1 binding. The c-Src K152R mutant (mutation of lysine 152 into arginine) impaired the resorption of bone by osteoclasts. These findings not only clarify the role of the RACK1-c-Src axis as a key regulator of osteoclast function but will also help to develop new antiresorption therapies to prevent bone loss-related diseases.

Original languageEnglish
Article number86
JournalExperimental and Molecular Medicine
Volume51
Issue number7
DOIs
StatePublished - 1 Jul 2019

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