Semaphorins are secreted and membrane bound proteins that regulate axon guidance through receptors Plexins and neuropilins. Plexin B1, the Semaphorin 4D receptor, is a recently described tumor suppressor protein for melanoma. We recently showed that Plexin B1 abrogates activation of the oncogenic receptor, c-Met, by its ligand, hepatocyte growth factor (HGF), in melanoma. We have now investigated the effect of Plexin B1 on integrin-dependent pp125(FAK) activation, and the small GTP-binding protein Rho, in melanoma. Integrin receptors and Rho play critical roles in melanoma progression, through regulation of migration, proliferation and apoptosis. We engineered two human melanoma cell lines expressing Plexin B1 and analyzed integrin-dependent migration, integrin-dependent pp125(FAK) activation, and Rho activity. Results show that Plexin B1 abrogates integrin-dependent migration and activation of pp125(FAK). We also show that Rho activity is significantly reduced in cells expressing Plexin B1, and that Plexin B1 suppresses HGF-dependent Rho activation.
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http://dx.doi.org/10.1111/j.1755-148X.2010.00797.x | DOI Listing |
Pigment Cell Melanoma Res
February 2011
Department of Dermatology, University of Rochester School of Medicine, Rochester, NY, USA.
Cell Signal
December 2008
Institute of Pharmacology, Toxicology and Pharmacy, University of Munich, Königinstrasse 16, D-80539 München, Germany.
Integrin-mediated cell adherence to extracellular matrix proteins results in stimulation of ERK1/2 activity, a mechanism involving focal adhesion tyrosine kinases (pp125FAK, Pyk-2) and epidermal growth factor receptors (EGFRs). G protein-coupled receptors (GPCRs) may also mediate ERK1/2 activation in an integrin-dependent manner, the underlying signaling mechanism of which still remains unclear. Here we demonstrate that the delta-opioid receptor (DOR), a typical GPCR, stimulates ERK1/2 activity in HEK293 cells via integrin-mediated transactivation of EGFR function.
View Article and Find Full Text PDFClin Appl Thromb Hemost
October 2005
Pró-Sangue Foundation, Heart Institute, School of Medicine, University of São Paulo, Brazil.
Despite of several lines of evidence indicating a pathophysiologic role of platelets in pulmonary hypertension, the occurrence of chronic endogenous platelet activation has been a matter of debate. It was hypothesized that the pattern of tyrosine phosphorylation of platelet proteins examined ex vivo could provide information on the state of platelet activation. This was examined in 10 patients with pulmonary arterial hypertension aged 18 to 53 years.
View Article and Find Full Text PDFPharmacol Res
March 2005
Department of Medicinal Chemistry, Medical Academy of Białystok, ul. Kilińskiego 1, 15-230 Białystok, Poland.
Prolidase [E.C. 3.
View Article and Find Full Text PDFOncogene
November 2003
Department of Toxicology, Institut für umweltmedizinische Forschung at the Heinrich-Heine-University Düsseldorf, Auf'm Hennekamp 50, 40225 Düsseldorf, Germany.
Integrin-mediated signalling has been implicated in asbestos-induced carcinogenesis. In studies here, we examined signal transduction events associated with integrin-directed cell reactions triggered by crocidolite asbestos in the pleural mesothelial cell line 4/4 RM-4. Crocidolite fibres induced a significant time- and dose-dependent activation of the extracellular-signal-regulated kinases ERK1 and ERK2.
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