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