Leupaxin is a critical adaptor protein in the adhesion zone of the osteoclast

Anandarup Gupta, Beth S. Lee, Mohammed A. Khadeer, Zhihui Tang, Meenakshi Chellaiah, Yousef Abu-Amer, Joshua Goldknopf, Keith A. Hruska

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54 Scopus citations


Leupaxin is a cytoskeleton adaptor protein that was first identified in human macrophages and was found to share homology with the focal adhesion protein, paxillin. Leupaxin possesses several protein-binding domains that have been implicated in targeting proteins such as focal adhesion kinase (pp125FAK) to focal adhesions. Leupaxin can be detected in monocytes and osteoclasts, both cells of hematopoietic origin. We have identified leupaxin to be a component of the osteoclast podosomal signaling complex. We have found that leupaxin in murine osteoclasts is associated with both PYK2 and pp125FAK in the osteoclast. Treatment of osteoclasts with TNF-α and soluble osteopontin were found to stimulate tyrosine phosphorylation of both leupaxin and leupaxin-associated PYK2. Leupaxin was found to co-immunoprecipitate with the protein tyrosine phosphatase PTP-PEST. The cellular distribution of leupaxin, PYK2, and protein tyrosine phosphorylation-PEST co-localized at or near the osteoclast podosomal complex. Leupaxin was also found to associate with the ARF-GTPase-activating protein, paxillin kinase linker p95PKL, thereby providing a link to regulators of cytoskeletal dynamics in the osteoclast. Overexpression of leupaxin by transduction into osteoclasts evoked numerous cytoplasmic projections at the leading edge of the cell, resembling a motile phenotype. Finally, in vitro inhibition of leupaxin expression in the osteoclast led to a decrease in resorptive capacity. Our data suggest that leupaxin may be a critical nucleating component of the osteoclast podosomal signaling complex.

Original languageEnglish
Pages (from-to)669-685
Number of pages17
JournalJournal of Bone and Mineral Research
Issue number4
StatePublished - Apr 1 2003


  • Leupaxin
  • Osteopontin
  • Paxillin kinase linker
  • Protein tyrosine phosphatase
  • Protein tyrosine phosphorylation
  • Protein-tyrosine kinase 2
  • TNF-α


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