Leupaxin Is a Critical Adaptor Protein in the Adhesion Zone of the Osteoclast

Abstract

Leupaxin is a cytoskeleton adaptor protein that was first identified in human macrophages

Leupaxin acts as a mediator in prostate carcinoma progression through deregulation of p120catenin expression

“…Applying two independent LPXN/TRAMP mouse lines, we could show for the first time that LPXN directly enhances the progression and metastasis of prostate cancer in vivo (Figures 1 and 2), whereas the onset of prostate lesions remained unaffected. These results are consistent with the data obtained from TAT-LPXN transduction studies in PCa cell lines presented here and from earlier studies, which show a higher migration and invasion rate as compared with control cells (Gupta et al, 2003;Sahu et al, 2007). In addition, primary cells isolated from both double transgenic LPXN/TRAMP and single transgenic TRAMP prostate tumours, respectively, support these observations in vitro.…”

“…In murine osteoclasts, FAK, PTP-PEST and p95PKL (paxillin kinase linker) could be identified as interaction partners of LPXN (Gupta et al, 2003). Recently, we identified LPXN as a protein, which is overexpressed in a subset of human prostate cancer specimens and a positive correlation between enhanced LPXN expression and tumour stage was depicted.…”

Leupaxin Negatively Regulates B Cell Receptor Signaling

“…Monoclonal antibodies against human leupaxin (283C and 315G) were obtained from Dr. A. Gupta (32) Cell Stimulation, Western Blotting, and Immunoprecipitations-Cells were resuspended in RPMI 1640 medium at 2 ϫ 10 6 cells/200 l and serum-starved at 37°C for 1 h prior to stimulation with anti-Ig antibodies. BJAB cells were stimulated with 10 g/ml anti-human IgM F(abЈ) 2 fragment, and A20 cells with 15 g/ml anti-mouse IgG F(abЈ) 2 fragment.…”

“…Both LD and LIM domains had been shown to be important for protein-protein interactions, and in addition, LIM domains have also been shown to play a role in the focal adhesion targeting of paxillin superfamily members (31). Recent works also established a role for leupaxin in the function of osteoclasts (32) and in the migration of prostate cancer cells (33). Leupaxin is known to interact with Pyk2 (29); Src (34); PEST domain tyrosine phosphatase (PEP) (35); and PTP-PEST, pp125 FAK , and the ADP-ribosylation factor (ARF) GTPase-activating protein p95 PKL (32); and some of these proteins are known to be expressed in B cells.…”

“…Recent works also established a role for leupaxin in the function of osteoclasts (32) and in the migration of prostate cancer cells (33). Leupaxin is known to interact with Pyk2 (29); Src (34); PEST domain tyrosine phosphatase (PEP) (35); and PTP-PEST, pp125 FAK , and the ADP-ribosylation factor (ARF) GTPase-activating protein p95 PKL (32); and some of these proteins are known to be expressed in B cells.…”