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A. H. Kakazu, H. E. P. Bazan; Protein Tyrosine Phosphatase 1B Modulates Erk1/2 Signaling and Cell Proliferation Stimulated by HGF in Corneal Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2720.
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© ARVO (1962-2015); The Authors (2016-present)
Hepatocyte growth factor (HGF) is the ligand for the c-Met receptor, expressed in corneal epithelial cells. HGF stimulates signaling pathways that promote proliferation, migration and cell survival of the cells (JBC 278:21989,2003; IOVS 45:3492,2004), activities that can be regulated by protein tyrosine phosphatases (PTP). We had previously reported that PTP1B bind to the c-Met receptor (ARVO 2006). Here we investigate if PTP1B regulates the phosphorylation (activation) of tyrosine residues of c-Met receptor and if it affects some of the downstream signals.
Human cornea epithelial cells (HCEC) were transfected with PTP1B- siRNA, then stimulated with HGF (40 ng/ml). Samples were analyzed by western blot for PTP1B, different tyrosine phosphorylated residues of c-Met, p-Akt, p-ERK1/2, and p-p70S6K. Cells were immunostained to localize PTP1B. Cell proliferation was also evaluated.
Immunocytochemistry showed PTP1B co-localized with the c-Met receptor in HCEC. Transfection of the cells with PTP1B-siRNA demonstrated a 60% decrease in PTP1B expression. Stimulation with HGF induced phosphorylation of c-Met at Tyr 1234, 1235, and 1349, but none of the activity of these residues were changed when PTP1B was knocked down. HGF activates ERK1/2 at 15 min that was further activated when PTP1B expression was decreased. Stimulation of HCEC for 40h with HGF increased cell proliferation that was further increase in the presence of PTP1B-siRNA
Our results suggest that PTP1B do not affect directly the phosphorylation of Tyr residues of c-Met, but increase the activation of ERK1/2 and the proliferation of the cells affected by this signaling pathway. It is possible that PTP1B is bound to an adapter protein of c-Met and modulates selective responses stimulated by HGF.
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