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J. Biol. Chem., Vol. 281, Issue 45, 34104-34112, November 10, 2006
Identification of a Filamin Docking Site on PTP-PEST*![]() ![]() ![]() ¶||1
From the
PTP-PEST is a cytoplasmic protein-tyrosine phosphatase (PTP) implicated in the regulation of biological processes such as cell motility, cytokinesis, focal adhesion disassembly, and lymphocyte activation. Using a proteomics approach, filamin-A was identified as a novel interacting protein that bound to GST-PTP-PEST. This interaction was confirmed in vitro and in cells by coimmunoprecipitation. The site of filamin interaction on PTP-PEST was mapped to the fourth proline-rich region (Pro4). PTP-PEST has previously been implicated in the regulation of cytokinesis. In further support of this finding, expression of PTP-PEST in HeLa cells resulted in the formation of multinucleated cells. A PTP-PEST mutant lacking Pro4 and unable to bind filamin-A failed to induce the multinucleated phenotype. Further, depletion of filamin-A in HeLa cells was found to reduce the PTP-PEST-dependent multinucleation phenotype. Hence, we conclude that the interaction of PTP-PEST with filamin-A may function in the control of cytokinesis in mammalian cells.
Received for publication, June 30, 2006 , and in revised form, September 12, 2006. * This project was supported by National Institutes of Health Grant CA90901 and HL45100 (to M. D. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 1 To whom correspondence should be addressed: 534 Taylor Hall, CB 7090, Dept. of Cell & Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599. Tel.: 919-966-0391; Fax: 919-966-1856; E-mail: crispy4{at}med.unc.edu.
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