title: Regulation of ERK1/2 activity upon contact inhibition in fibroblasts.
abstract: Contact inhibition is a crucial mechanism regulating proliferation in vitro and in vivo. Despite its generally accepted importance for maintaining tissue homeostasis knowledge about the underlying molecular mechanisms of contact inhibition is still scarce. Since the MAPK ERK1/2 plays a pivotal role in the control of proliferation, we investigated regulation of ERK1/2 phosphorylation which is downregulated in confluent NIH3T3 cultures. We found a decrease in upstream signaling including phosphorylation of the growth factor receptor adaptor protein ShcA and the MAPK kinase MEK1/2 in confluent compared to exponentially growing cultures whereas involvement of ERK1/2 phosphatases in ERK1/2 inactivation is unlikely. Treatment of confluent, serum-deprived cultures with PDGF-B resulted in similar phosphorylation of ERK1/2 and induction of DNA-synthesis as detected in sparse, serum-deprived cultures. In contrast, ERK1/2 phosphorylation and DNA-synthesis could not be stimulated in confluent, serum-deprived cultures exposed to EGF. Our data indicate that PDGFR- and EGFR signaling are differentially inhibited in confluent cultures of NIH3T3 cells.
authors.affiliation: Institute of Toxicology, University Medical Center of the Johannes Gutenberg-University, 55131 Mainz, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Küppers
authors.forename: Dagmar
authors.initials: D
authors.lastname: Faust
authors.forename: Berenike
authors.initials: B
authors.lastname: Linz
authors.forename: Cornelia
authors.initials: C
authors.lastname: Dietrich
mesh_terms: D000818:Animals; D002450:Cell Communication; D049109:Cell Proliferation; D015536:Down-Regulation; D066246:ErbB Receptors / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000494:pharmacology; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism
chemical_list: D066246:ErbB Receptors; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3