HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 292/6/C2288    most recent 00503.2006v1 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 ISI 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 ISI Web of Science (1) 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.

EXTRACELLULAR MATRIX, CELL INTERACTIONS

Interaction of Pyk2 and PTP-PEST with leupaxin in prostate cancer cells

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

Submitted 25 September 2006 ; accepted in final form 28 January 2007

We have identified the presence of leupaxin (LPXN), which belongs to the paxillin extended family of focal adhesion-associated adaptor proteins, in prostate cancer cells. Previous studies have demonstrated that LPXN is a component of the podosomal signaling complex found in osteoclasts, where LPXN was found to associate with the protein tyrosine kinases Pyk2 and c-Src and the cytosolic protein tyrosine phosphatase-proline-, glutamate-, serine-, and threonine-rich sequence (PTP-PEST). In the current study, LPXN was detectable as a 50-kDa protein in PC-3 cells, a bone-derived metastatic prostate cancer cell line. In PC-3 cells, LPXN was also found to associate with Pyk2, c-Src, and PTP-PEST. A siRNA-mediated inhibition of LPXN resulted in decreased in vitro PC-3 cell migration. A recombinant adenoviral-mediated overexpression of LPXN resulted in an increased association of Pyk2 with LPXN, whereas a similar adenoviral-mediated overexpression of PTP-PEST resulted in decreased association of Pyk2 and c-Src with LPXN. The overexpression of LPXN in PC-3 cells resulted in increased migration, as assessed by in vitro Transwell migration assays. On the contrary, the overexpression of PTP-PEST in PC-3 cells resulted in decreased migration. The overexpression of LPXN resulted in increased activity of Rho GTPase, which was decreased in PTP-PEST-overexpressing cells. The increase in Rho GTPase activity following overexpression of LPXN was inhibited in the presence of Y27632, a selective inhibitor of Rho GTPase. In conclusion, our data demonstrate that LPXN forms a signaling complex with Pyk2, c-Src, and PTP-PEST to regulate migration of prostate cancer cells.

PC-3; protein tyrosine phosphatase-proline-, glutamate-, serine-, and threonine-rich sequence; c-Src; migration

This article has been cited by other articles:

				L. J. Sundberg-Smith, L. A. DiMichele, R. L. Sayers, C. P. Mack, and J. M. Taylor The LIM Protein Leupaxin Is Enriched in Smooth Muscle and Functions As an Serum Response Factor Cofactor to Induce Smooth Muscle Cell Gene Transcription Circ. Res., June 20, 2008; 102(12): 1502 - 1511. [Abstract] [Full Text] [PDF]