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J. Cell Biol.,
Volume 144, Number 5, March 8, 1999 1019-1031

* Department of Biochemistry, McGill University, Montréal, Québec, Canada H3G 1Y6; In this article, we show that, in transfected
COS-1 cells, protein tyrosine phosphatase (PTP)-PEST
translocates to the membrane periphery following stimulation by the extracellular matrix protein fibronectin.
When plated on fibronectin, PTP-PEST (
Center for Cancer Research,
Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; and § Department of Molecular Oncology, Genentech,
Inc., South San Francisco, California 94080
/
) fibroblasts display a strong defect in motility. 3 h after plating on fibronectin, the number and size of vinculin containing focal adhesions were greatly increased in the
homozygous PTP-PEST mutant cells as compared with
heterozygous cells. This phenomenon appears to be due
in part to a constitutive increase in tyrosine phosphorylation of p130CAS, a known PTP-PEST substrate, paxillin, which associates with PTP-PEST in vitro, and focal
adhesion kinase (FAK). Another effect of this constitutive hyperphosphorylation, consistent with the focal adhesion regulation defect, is that (
/
) cells spread
faster than the control cell line when plated on fibronectin. In the PTP-PEST (
/
) cells, an increase in
affinity for the SH2 domains of Src and Crk towards
p130CAS was also observed. In (
/
) cells, we found a
significant increase in the level of tyrosine phosphorylation of PSTPIP, a cleavage furrow-associated protein
that interacts physically with all PEST family members.
An effect of PSTPIP hyperphosphorylation appears to
be that some cells remain attached at the site of the
cleavage furrow for an extended period of time. In conclusion, our data suggest PTP-PEST plays a dual role in
cell cytoskeleton organization, by promoting the turnover of focal adhesions required for cell migration, and
by directly or indirectly regulating the proline, serine,
threonine phosphatase interacting protein (PSTPIP) tyrosine phosphorylation level which may be involved in
regulating cleavage furrow formation or disassembly
during normal cell division.
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