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MAP kinase and beta-catenin signaling in HGF induced RPE migration.
Mol Vis. 2002 Dec 20; 8:483-93.MV

Abstract

PURPOSE

Hepatocyte growth factor (HGF) has been implicated in retinal pigment epithelial (RPE) cell proliferation and migration that occurs in proliferative retinal diseases such as proliferative vitreoretinopathy (PVR). The aim of this study is to investigate HGF induced signaling pathways that lead to RPE cell migration.

METHODS

Localization of beta-catenin was determined by immunofluorescence. HGF induced migration of ARPE-19 cells was studied using a quantitative migration assay after wounding in the presence of a DNA polymerase inhibitor, and in the presence or absence of a mitogen activated protein kinase (MAP kinase) kinase inhibitor. C-jun expression was determined by semi-quantitative RT-PCR and by Northern blot analysis. P42/p44 MAP kinase activity was determined by western blot and by an immunoprecipitation kinase assay. Tyrosine phosphorylation of the HGF receptor (HGFR or c-met) and beta-catenin was determined by immunoprecipitation and western blot analysis. Transactivation activity of beta-catenin was determined by luciferase reporter gene analysis.

RESULTS

Beta-catenin and E-cadherin were co-localized on the basal surface of the RPE in vivo. Diffusion of the cell surface-localized beta-catenin occurs in migratory cells in vitro in the presence of HGF. HGF induced a MAP kinase dependent ARPE-19 cell migration, which is accompanied with a transient increase of c-jun expression and concomitant increases of MAP kinase activity, tyrosine phosphorylation of HGFR and beta-catenin, increased cytosolic levels of beta-catenin, and transactivation activity of beta-catenin. Tyrosine phosphorylation of HGFR and beta-catenin occurs in the primary or passaged RPE cultures or proliferative ARPE-19 cells, but not freshly isolated RPE or differentiated ARPE-19 cells.

CONCLUSIONS

This study defines the signal transduction pathways activated by HGF in RPE cells, leading to an increase in the MAP kinase activity and free pool of beta-catenin, and changes in gene expression. These findings are consistent with the hypothesis that both beta-catenin and MAP kinases are components of the HGF induced RPE migration that occurs in proliferative retinal diseases.

Authors+Show Affiliations

Department of Ophthalmology, Medical College of Georgia, Augusta, GA 30912, USA. giliou@mail.mcg.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12500177

Citation

Liou, Gregory I., et al. "MAP Kinase and Beta-catenin Signaling in HGF Induced RPE Migration." Molecular Vision, vol. 8, 2002, pp. 483-93.
Liou GI, Matragoon S, Samuel S, et al. MAP kinase and beta-catenin signaling in HGF induced RPE migration. Mol Vis. 2002;8:483-93.
Liou, G. I., Matragoon, S., Samuel, S., Behzadian, M. A., Tsai, N. T., Gu, X., Roon, P., Hunt, D. M., Hunt, R. C., Caldwell, R. B., & Marcus, D. M. (2002). MAP kinase and beta-catenin signaling in HGF induced RPE migration. Molecular Vision, 8, 483-93.
Liou GI, et al. MAP Kinase and Beta-catenin Signaling in HGF Induced RPE Migration. Mol Vis. 2002 Dec 20;8:483-93. PubMed PMID: 12500177.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MAP kinase and beta-catenin signaling in HGF induced RPE migration. AU - Liou,Gregory I, AU - Matragoon,Suraporn, AU - Samuel,Sara, AU - Behzadian,M Ali, AU - Tsai,Nai-Tse, AU - Gu,Xiaolin, AU - Roon,Penny, AU - Hunt,D Margaret, AU - Hunt,Richard C, AU - Caldwell,Ruth B, AU - Marcus,Dennis M, Y1 - 2002/12/20/ PY - 2002/12/25/pubmed PY - 2002/12/31/medline PY - 2002/12/25/entrez SP - 483 EP - 93 JF - Molecular vision JO - Mol. Vis. VL - 8 N2 - PURPOSE: Hepatocyte growth factor (HGF) has been implicated in retinal pigment epithelial (RPE) cell proliferation and migration that occurs in proliferative retinal diseases such as proliferative vitreoretinopathy (PVR). The aim of this study is to investigate HGF induced signaling pathways that lead to RPE cell migration. METHODS: Localization of beta-catenin was determined by immunofluorescence. HGF induced migration of ARPE-19 cells was studied using a quantitative migration assay after wounding in the presence of a DNA polymerase inhibitor, and in the presence or absence of a mitogen activated protein kinase (MAP kinase) kinase inhibitor. C-jun expression was determined by semi-quantitative RT-PCR and by Northern blot analysis. P42/p44 MAP kinase activity was determined by western blot and by an immunoprecipitation kinase assay. Tyrosine phosphorylation of the HGF receptor (HGFR or c-met) and beta-catenin was determined by immunoprecipitation and western blot analysis. Transactivation activity of beta-catenin was determined by luciferase reporter gene analysis. RESULTS: Beta-catenin and E-cadherin were co-localized on the basal surface of the RPE in vivo. Diffusion of the cell surface-localized beta-catenin occurs in migratory cells in vitro in the presence of HGF. HGF induced a MAP kinase dependent ARPE-19 cell migration, which is accompanied with a transient increase of c-jun expression and concomitant increases of MAP kinase activity, tyrosine phosphorylation of HGFR and beta-catenin, increased cytosolic levels of beta-catenin, and transactivation activity of beta-catenin. Tyrosine phosphorylation of HGFR and beta-catenin occurs in the primary or passaged RPE cultures or proliferative ARPE-19 cells, but not freshly isolated RPE or differentiated ARPE-19 cells. CONCLUSIONS: This study defines the signal transduction pathways activated by HGF in RPE cells, leading to an increase in the MAP kinase activity and free pool of beta-catenin, and changes in gene expression. These findings are consistent with the hypothesis that both beta-catenin and MAP kinases are components of the HGF induced RPE migration that occurs in proliferative retinal diseases. SN - 1090-0535 UR - https://www.unboundmedicine.com/medline/citation/12500177/MAP_kinase_and_beta_catenin_signaling_in_HGF_induced_RPE_migration_ L2 - http://www.molvis.org/molvis/v8/a59/ DB - PRIME DP - Unbound Medicine ER -