Functional characterization of receptor‐type protein tyrosine phosphatase CD148 (HPTPη/DEP‐1) in Fcγ receptor IIa signal transduction of human neutrophils

Hundt, Matthias; Schmidt, Reinhold

doi:10.1002/eji.1830271255

Cited by 14 publications

(8 citation statements)

References 16 publications

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“…Upregulation of DEP-1 expression at high cell densities in WI-38 human embryonic lung fibroblasts and upon cell differentiation of ZR75 mammary carcinoma cells as well as low expression levels in thyroid tumors compared to normal thyroid tissue may indicate a possible negative role of DEP-1 in regulation of cell proliferation and transformation. Consistent with such a role, DEP-1 expression in mammary carcinoma cell lines and in thyroid carcinoma cells suppresses the transformed phenotype (Keane et al, 1996;Hundt and Schmidt, 1997;Zhang et al, 1997;Tangye et al, 1998a;Iuliano et al, 2003). Recently, positional cloning of the mouse colon cancer susceptibility gene Scc1 revealed its identity with PTPRJ, encoding murine DEP-1.…”

Section: Introductionmentioning

confidence: 84%

The protein-tyrosine phosphatase DEP-1 modulates growth factor-stimulated cell migration and cell–matrix adhesion

et al. 2003

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Density-enhanced protein-tyrosine phosphatase-1 (DEP-1 also CD148) is a transmembrane molecule with a single intracellular PTP domain. It has recently been proposed to function as a tumor suppressor. We have previously shown that DEP-1 dephosphorylates the activated plateletderived growth factor (PDGF) b-receptor in a siteselective manner (Kovalenko et al. (2000). J. Biol. Chem. 275, 16219-16226). We analysed cell lines with inducible DEP-1 expression for cellular functions of DEP-1. Several aspects of PDGFb-receptor signaling were negatively affected by DEP-1 expression. These include PDGFstimulated activation of inositol trisphosphate formation, Erk1/2, p21Ras, and Src. Activation of receptor-associated phosphoinositide-3 kinase activity and of Akt/PKB were weakly attenuated at early time points of stimulation. Inhibition of PDGF-stimulated signaling depended on DEP-1 catalytic activity. Importantly, DEP-1 inhibited PDGF-stimulated cell migration. The catalytically inactive DEP-1 C1239S variant enhanced cell migration and PDGF-stimulated Erk1/2 activation, suggesting a dominant negative interference with endogenous DEP-1. In contrast to cell migration, cell-substrate adhesion was promoted by active DEP-1 and delayed or suppressed by DEP-1 C1239S, correlating with positive effects of DEP-1 on adhesion-stimulated Src kinase. We propose that negative regulation of growth-factor stimulated cell migration and promotion of cell-matrix adhesion may be related to the function of DEP-1 as tumor suppressor.

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Section: Introductionmentioning

confidence: 84%

The protein-tyrosine phosphatase DEP-1 modulates growth factor-stimulated cell migration and cell–matrix adhesion

et al. 2003

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“…DEP-1 is expressed at low levels in resting T cells, but is upregulated in activated T cells, and ligation with anti-DEP-1 antibodies induces proliferation of anti-CD3 activated T cells (Tangye et al, 1998a). Interestingly, transient transfection of DEP-1 has been reported to be a negative regulator of T cell activation, and also results in a reduction of TCR-mediated ERK-1 and ERK-2 activation, and reduced tyrosine phosphorylation (Palou et al, 1997;Hundt et al, 1997;Tangye et al, 1998a;Tangye et al, 1998b;Billard et al, 2000;del Pozo et al, 2000). DEP-1…”

Section: Introductionmentioning

confidence: 99%

The tyrosine phosphatase DEP-1 induces cytoskeletal rearrangements, aberrant cell-substratum interactions and a reduction in cell proliferation

Kellie

Craggs

Bird

et al. 2004

Journal of Cell Science

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The receptor protein tyrosine phosphatase density-enhanced phosphatase-1 (DEP-1) has been implicated in aberrant cancer cell growth and immune cell function, however, its function within cells has yet to be properly elucidated. To investigate the cellular function of DEP-1, stable cell lines inducibly expressing DEP-1 were generated. Induction of DEP-1 expression was found to decrease PDGF-stimulated tyrosine phosphorylation of a number of cellular proteins including the PDGF receptor, and to inhibit growth factor-stimulated phosphorylation of components of the MAPK pathway, indicating that DEP-1 antagonised PDGF receptor signalling. This was supported by data showing that DEP-1 expression resulted in a reduction in cell proliferation. DEP-1-expressing cells had fewer actin-containing microfilament bundles, reduced vinculin and paxillin-containing adhesion plaques, and were defective in interactions with fibronectin. Defective cell-substratum adhesion correlated with lack of activation of FAK in DEP-1-expressing cells. Time-lapse interference reflection microscopy of live cells revealed that although small focal contacts at the leading edge were generated in DEP-1-expressing cells, they failed to mature into stable focal adhesions, as found in control cells. Further motility analysis revealed that DEP-1-expressing cells retained limited random motility, but showed no chemotaxis towards a gradient of PDGF. In addition, cell-cell contacts were disrupted, with a change in the localisation of cadherin from discrete areas of cell-cell contact to large areas of membrane interaction, and there was a parallel redistribution of β-catenin. These results demonstrate that DEP-1 is a negative regulator of cell proliferation, cell-substratum contacts, motility and chemotaxis in fibroblasts.

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“…Two receptor-type tyrosine phosphatases CD45 and CD148 are known to modulate the functional responses to CD32 cross-linking in neutrophils (27,28). Additionally, the soluble phosphatases SHP-1 and SHP-2 are both present in neutrophils.…”

Section: Discussionmentioning

confidence: 99%

“…Overall, neutrophil PTP activity has been shown to decrease following stimulation with FMLP or phorbol esters (25,26). Two membrane receptor-like PTPs, CD45 and CD148, have been linked to the regulation of neutrophil responses (27,28). However, the role of soluble PTP in neutrophil signal transduction is poorly understood although two Src homology (SH) 2-containing phosphatases, namely, SHP-1 (29) and SHP-2 (30) are present in neutrophils.…”

Section: Modulation Of Human Neutrophil Responses To Cd32mentioning

confidence: 99%

Modulation of Human Neutrophil Responses to CD32 Cross-Linking by Serine/Threonine Phosphatase Inhibitors: Cross-Talk Between Serine/Threonine and Tyrosine Phosphorylation

Rollet-Labelle

Gilbert

Naccache

2000

The Journal of Immunology

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The interplay between serine/threonine and tyrosine phosphorylation was studied in human neutrophils. The direct effects of calyculin and okadaic acid, potent inhibitors of PP1 and PP2A serine/threonine phosphatases, on the patterns of neutrophil phosphorylation, and their effects on the responses of neutrophils to CD32 cross-linking were monitored. After a 2-min incubation with 10−6 M calyculin, a transient tyrosine phosphorylation of a subset of proteins, among which Cbl and Syk, was observed. After a longer incubation (>5 min) with calyculin, concomitant with an accumulation of serine and threonine phosphorylation, neutrophil responses to CD32 cross-linking were selectively altered. Tyrosine phosphorylation of Cbl in response to CD32 cross-linking was inhibited by calyculin, and this inhibition was linked with a slower electrophoretic mobility of Cbl as a consequence of its phosphorylation on serine/threonine residues. However, tyrosine phosphorylation of Syk and of the receptor itself were not affected. Furthermore, the mobilization of intracellular calcium stimulated by CD32 cross-linking was totally abrogated by calyculin. Finally, the stimulation of superoxide production observed in response to CD32 cross-linking was enhanced in calyculin-treated cells. These results suggest that serine/threonine phosphorylation events regulate the signaling pathways activated by CD32 cross-linking in neutrophils and identify a novel mechanism of modulation of the functional responsiveness of human neutrophils to CD32 cross-linking.

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Functional characterization of receptor‐type protein tyrosine phosphatase CD148 (HPTPη/DEP‐1) in Fcγ receptor IIa signal transduction of human neutrophils

Cited by 14 publications

References 16 publications

The protein-tyrosine phosphatase DEP-1 modulates growth factor-stimulated cell migration and cell–matrix adhesion

The protein-tyrosine phosphatase DEP-1 modulates growth factor-stimulated cell migration and cell–matrix adhesion

The tyrosine phosphatase DEP-1 induces cytoskeletal rearrangements, aberrant cell-substratum interactions and a reduction in cell proliferation

Modulation of Human Neutrophil Responses to CD32 Cross-Linking by Serine/Threonine Phosphatase Inhibitors: Cross-Talk Between Serine/Threonine and Tyrosine Phosphorylation

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