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Originally published In Press as doi:10.1074/jbc.M206407200 on September 13, 2002

J. Biol. Chem., Vol. 277, Issue 48, 46659-46668, November 29, 2002
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The Tyrosine Phosphatase PRL-1 Localizes to the Endoplasmic Reticulum and the Mitotic Spindle and Is Required for Normal Mitosis*

Jing Wang, Celeste E. Kirby, and Ronald HerbstDagger

From the DNAX Research Institute, Palo Alto, California 94304

PRL-1 is one of three closely related protein-tyrosine phosphatases, which are characterized by C-terminal farnesylation. Recent reports suggest that they are involved in the regulation of cell proliferation and transformation. However, their biological function has not yet been determined. Here we show that PRL-1 mRNA is overexpressed in a number of human tumor cell lines, including HeLa cells. Using immunofluorescence we studied the subcellular localization of endogenous PRL-1, and our results demonstrate that PRL-1 exhibits cell cycle-dependent localization; in non-mitotic HeLa cells, PRL-1 is localized to the endoplasmic reticulum in a farnesylation-dependent manner. In mitotic cells PRL-1 relocalizes to the centrosomes and the spindle apparatus, proximal to the centrosomes, in a farnesylation-independent manner. Conditional expression of a catalytic domain mutant in HeLa cells results in a delay in the progression of cells through mitosis but has no effect on other phases of the cell cycle. Further, expression of a farnesylation site PRL-1 mutant results in mitotic defects, characterized by chromosomal bridges in anaphase and lagging chromosomes, without affecting spindle checkpoint function. Together, these results suggest that PRL-1 function is regulated in a cell cycle-dependent manner and implicate PRL-1 in regulating progression through mitosis, possibly by modulating spindle dynamics.


* The DNAX Research Institute is fully supported by the Schering-Plough Corporation.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: DNAX Research Inst., 901 California Ave., Palo Alto, CA 94304. Tel.: 650-496-1245; Fax: 650-496-1200; E-mail: ronald.herbst@dnax.org.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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