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This Article Full Text Full Text (PDF) All Versions of this Article: 292/1/C581    most recent 00636.2005v2 00636.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Sahu, S. N. Articles by Gupta, A. Search for Related Content PubMed PubMed Citation Articles by Sahu, S. N. Articles by Gupta, A.

PROTEIN AND VESICLE TRAFFICKING, CYTOSKELETON

Association of leupaxin with Src in osteoclasts

¹Department of Biomedical Sciences, Dental School, University of Maryland, Baltimore; and ²Biochemistry and Molecular Biology, University of Maryland, Baltimore County, Maryland

Submitted 19 December 2005 ; accepted in final form 11 August 2006

Leupaxin (LPXN), which belongs to the paxillin extended family of adaptor proteins, was previously identified as a component of the sealing zone in osteoclasts. LPXN was found to associate with several podosomal proteins, such as the protein tyrosine kinase Pyk2, the protein-tyrosine phosphatase-PEST (PTP-PEST), actin-binding proteins, and regulators of actin cytoskeletal reorganization. It was previously demonstrated that inhibition of LPXN expression resulted in reduced osteoclast-mediated resorption. In the current study, overexpression of LPXN in murine osteoclasts resulted in both enhanced resorptive activity and cell adhesion, as assessed by in vitro resorption assays. The overexpression of LPXN resulted in an increased association of Pyk2 with LPXN. In an attempt to determine an additional biochemical basis for the observed phenomenon in increased osteoclast activity, a coimmunoprecipitation screen for additional binding partners revealed that Src, a protein tyrosine kinase that is critical to both podosome formation and osteoclast function, was also associated with LPXN. After exposure to the pro-inflammatory and osteoclastogenic cytokine TNF-, there was an increase in the level of Src that coimmunoprecipitated with LPXN. Our data indicate that association of the scaffold protein LPXN with Src adds further complexity to the organization of the podosomal signaling complex in osteoclasts.

LPXN; sealing zone; podosomes; LD2 domain

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