Abstract
Low M(r) phosphotyrosine protein phosphatase interferes in vivo with the activation of several growth factor receptors and is transiently redistributed, following cell stimulation with platelet-derived growth factor, from the cytosol to the cytoskeleton. We demonstrate here that this phosphatase also participates in the regulation of cell spreading and migration, pointing to its involvement in cytoskeleton organization. Low M(r) phosphotyrosine protein phosphatase-overexpressing fibroblasts are, indeed, less spread than controls and display a significantly decreased number of focal adhesions and increased cell motility. Furthermore, p125 focal adhesion kinase is associated to, and dephosphorylated by, low M(r) phosphotyrosine protein phosphatase both in vitro and in vivo. This event is consistent with an altered association of pp60(src) with focal adhesion kinase. The activation of extracellular signal-regulated kinase, another well known event downstream of the focal adhesion kinase, is also affected. On the other hand, cells overexpressing the dominant-negative form of low M(r) phosphotyrosine protein phosphatase exhibit hyperphosphorylated focal adhesion kinase, reduced motility, and an increased number of focal adhesions, which are distributed all over the ventral cell surface. Taken together, the results reported here are in keeping with low M(r) phosphotyrosine protein phosphatase participation in FAK-mediated focal adhesion remodeling.
Highlights
Cell adhesion and motility are based on the organization and remodeling of macromolecular complexes called focal adhesions
The results reported here are in keeping with low Mr phosphotyrosine protein phosphatase participation in focal adhesion kinase (FAK)-mediated focal adhesion remodeling
With the experiments reported in this study, we investigated the role of LMW-PTP in cytoskeleton dynamics under adhesion stimuli only, in the absence of acute growth factor stimulation, and demonstrated that unphosphorylated LMW-PTP dephosphorylates FAK, participating in focal adhesion remodeling
Summary
Cell adhesion and motility are based on the organization and remodeling of macromolecular complexes called focal adhesions. In contrast to the above findings, fibroblasts expressing an inactive form of the SHP2 tyrosine phosphatase [15] or deficient in PTP-PEST [16] exhibit elevated tyrosine phosphorylation of FAK, an increase in number and size of focal adhesions, and decreased rates of cell migration. Following PDGF stimulation, LMW-PTP level transiently increases in the Triton-insoluble fraction, at the expense of the cytosol. This redistribution does not seem critical for LMW-PTP activity on growth factor receptors as neither fibroblast growth factor nor macrophage colony-stimulating factor induces enzyme redistribution, their activated receptors are substrates of LMW-PTP [20]. With the experiments reported in this study, we investigated the role of LMW-PTP in cytoskeleton dynamics under adhesion stimuli only, in the absence of acute growth factor stimulation, and demonstrated that unphosphorylated LMW-PTP dephosphorylates FAK, participating in focal adhesion remodeling
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