Biomedical subjects

M Sörby

Publications and source records attributed to M Sörby.

3 recordsLinked to original sources

PubMed2001

An extracellular ligand increases the specific activity of the receptor-like protein tyrosine phosphatase DEP-1.

Cellular growth, differentiation and migration is regulated by protein tyrosine phosphorylation. Receptor-like protein tyrosine phosphatases are thus likely to be key regulators of vital cellular processes. The regulation of these enzymes is in general poorly understood. Ligands have been identified only for a small subset of the receptor-like protein tyrosine phosphatases and in no case has upregulation of the specific activity by extracellular ligands been demonstrated. Prompted by earlier findings of ligands for receptor-like protein tyrosine phosphatases in extracellular matrix we investigated if Matrigel, a preparation of extracellular matrix proteins, contained modulators of the specific activity of the receptor-like protein tyrosine phosphatase DEP-1. Matrigel stimulation of cells increased the specific activity of immunoprecipitated DEP-1. Also, incubation of immunoprecipitated DEP-1 with Matrigel led to an increase in DEP-1 activity, which was blocked by soluble DEP-1 extracellular domain. Finally, immunoprecipitated DeltaECD-DEP-1, a mutant form of DEP-1 lacking most of the extracellular domain, failed to respond to Matrigel stimulation. These experiments identify Matrigel as a source of DEP-1 agonist(s) and provide the first evidence for upregulation of the specific activity of receptor-like protein tyrosine phosphatases by extracellular ligands.

Animals↗

PubMed1997

Cell scattering and migration induced by autocrine transforming growth factor alpha in human glioma cells in vitro.

In the present investigation, we have transfected a human malignant glioma cell line, U-1242 MG, and derived clones that produce transforming growth factor alpha (TGF-alpha) in an inducible manner using the tetracycline suppressible vector system. TGF-alpha expression was confirmed by Northern analysis, by ELISA, and by immunoprecipitation of metabolically labeled cells. The functional activity of the induced protein was proven by the finding of epidermal growth factor receptor (EGFR) tyrosine phosphorylation on induction of TGF-alpha. A clear effect on cell motility, i.e., cell scattering and an increased phagokinetic track area of individual glioma cells, was demonstrated. The fact that the EGFR tyrosine kinase activation was independent of cell density suggests that autocrine activation of the EGFR kinase occurred at the single-cell level. These findings are of interest, because increased cell motility is most likely a requirement for glioma cell invasion in vivo. The results imply that as a result of coexpression of EGFR and its ligand, individual glioma cells are capable of acting as independent autocrine locomotory units.

Antibodies, Monoclonal↗

PubMed1996

Protein-tyrosine phosphatase-mediated decrease of epidermal growth factor and platelet-derived growth factor receptor tyrosine phosphorylation in high cell density cultures.

Contact-induced growth inhibition is a characteristic feature of normal cells grown in monolayer. The importance of reversible tyrosine phosphorylation in mitogenic signaling, together with earlier reports of increased levels of protein-tyrosine phosphatases (PTPs) in densely cultured cells, has led to the proposal that PTPs may be involved in mediating contact inhibition of cell growth. We have compared net levels of ligand-induced tyrosine phosphorylation of the epidermal growth factor (EGF) receptor in mink lung epithelial cells cultured under sparse or dense conditions. The levels of net tyrosine phosphorylation of the stimulated EGF receptor was found to be more than 4-fold higher in sparse cultures. This difference was greatly reduced when cells were pretreated with the PTP inhibitor phenyl arsine oxide. Monitoring of dephosphorylation rates in vivo of the stimulated EGF receptors revealed increased EGF receptor-directed PTP activity in dense cultures. The platelet-derived growth factor beta-receptor, expressed in stably transfected porcine aortic endothelial cells, also displayed lower levels of ligand induced net tyrosine phosphorylation in cells from dense cultures. This density-dependent difference in tyrosine phosphorylation was reduced by pretreatment of cultures with the PTP inhibitor orthovanadate. A PTP-mediated decrease of the in vivo net levels of ligand induced tyrosine phosphorylation of EGF and platelet-derived growth factor receptors in cells at high density have thus been demonstrated. Loss of this previously unnoticed regulatory pathway may be involved in cellular transformation.

Animals↗