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Titolo:
Mechanism in the sequential control of cell morphology and S phase entry by epidermal growth factor involves distinct MEK/ERK activations
Autore:
Rescan, C; Coutant, A; Talarmin, H; Theret, N; Glaise, D; Guguen-Guillouzo, C; Baffet, G;
Indirizzi:
Hop Pontchaillou, Inst Fed Rech 97, Unite Rech Hepatol, INSERM,U522, F-35033 Rennes, France Hop Pontchaillou Rennes France F-35033 SERM,U522, F-35033 Rennes, France Fac Med, U456, F-35033 Rennes, France Fac Med Rennes France F-35033Fac Med, U456, F-35033 Rennes, France
Titolo Testata:
MOLECULAR BIOLOGY OF THE CELL
fascicolo: 3, volume: 12, anno: 2001,
pagine: 725 - 738
SICI:
1059-1524(200103)12:3<725:MITSCO>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
ADULT-RAT HEPATOCYTES; PROTEIN-KINASE KINASE; FOCAL ADHESION KINASE; MAP KINASE; CYCLIN D1; LIVER-REGENERATION; EXTRACELLULAR-MATRIX; PRIMARY CULTURES; SMOOTH-MUSCLE; DNA-SYNTHESIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: Baffet, G Hop Pontchaillou, Inst Fed Rech 97, Unite Rech Hepatol, INSERM,U522, F-35033 Rennes, France Hop Pontchaillou Rennes France F-35033 F-35033 Rennes, France
Citazione:
C. Rescan et al., "Mechanism in the sequential control of cell morphology and S phase entry by epidermal growth factor involves distinct MEK/ERK activations", MOL BIOL CE, 12(3), 2001, pp. 725-738

Abstract

Cell shape plays a role in cell growth, differentiation, and death. Herein, we used the hepatocyte, a normal, highly differentiated cell characterized by a long G1 phase, to understand the mechanisms that link cell shape to growth. First, evidence was provided that the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) cascade is a key transduction pathway controlling the hepatocyte morphology. MEK2/ERK2 activation in early Gl phase did not lead to cell proliferation but induced cell shape spreading and demonstration was provided that this MAPK-dependentspreading was required for reaching G1/S transition and DNA replication. Moreover, epidermal growth factor (EGF) was found to control this morphogenic signal in addition to its mitogenic effect. Thus, blockade of cell spreading by cytochalasin D or PD98059 treatment resulted in inhibition of EGF-dependent DNA replication. Our data led us to assess the first third of G1, is exclusively devoted to the growth factor-dependent morphogenic events, whereas the mitogenic signal occured at only approximately mid-Gl phase. Moreover, these two growth factor-related sequential signaling events involved successively activation of MEK2-ERK2 and then MEK1/2-ERK1/2 isoforms. In addition, we demonstrated that inhibition of extracellular matrix receptor, such as integrin beta1 subunit, leads to cell arrest in G1, whereas EGF was found to up-regulated integrin beta1 and fibronectin in a MEK-ERK- dependent manner. This process in relation to cytoskeletal reorganization could induce hepatocyte spreading, making them permissive for DNA replication. Our results provide new insight into the mechanisms by which a growth factor cantemporally control dual morphogenic and mitogenic signals during the G1 phase.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 01:31:54