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Titolo:
EGF RECEPTOR REGULATION OF CELL MOTILITY - EGF INDUCES DISASSEMBLY OFFOCAL ADHESIONS INDEPENDENTLY OF THE MOTILITY-ASSOCIATED PLC-GAMMA SIGNALING PATHWAY
Autore:
XIE H; PALLERO MA; GUPTA K; CHANG P; WARE MF; WITKE W; KWIATKOWSKI DJ; LAUFFENBURGER DA; MURPHYULLRICH JE; WELLS A;
Indirizzi:
UNIV ALABAMA,DEPT PATHOL BIRMINGHAM AL 35294 UNIV ALABAMA,DEPT PATHOL BIRMINGHAM AL 35294 VET ADM MED CTR BIRMINGHAM AL 35294 MIT,DEPT CHEM ENGN CAMBRIDGE MA 02139 MIT,CTR BIOMED ENGN CAMBRIDGE MA 02139 BRIGHAM & WOMENS HOSP,DEPT MED,DIV EXPT MED BOSTON MA 02115
Titolo Testata:
Journal of Cell Science
, volume: 111, anno: 1998,
parte:, 5
pagine: 615 - 624
SICI:
0021-9533(1998)111:<615:ERROCM>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
GROWTH-FACTOR RECEPTOR; SMOOTH-MUSCLE CELLS; PROTEIN-KINASE; EXTRACELLULAR-MATRIX; PHOSPHOLIPASE-C; TYROSINE PHOSPHORYLATION; VINCULIN DISTRIBUTION; CARCINOMA-CELLS; MIGRATION; INTEGRIN;
Keywords:
MIGRATION; EGF RECEPTOR; ADHESION; FOCAL CONTACT; CELL-MATRIX INTERACTION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
58
Recensione:
Indirizzi per estratti:
Citazione:
H. Xie et al., "EGF RECEPTOR REGULATION OF CELL MOTILITY - EGF INDUCES DISASSEMBLY OFFOCAL ADHESIONS INDEPENDENTLY OF THE MOTILITY-ASSOCIATED PLC-GAMMA SIGNALING PATHWAY", Journal of Cell Science, 111, 1998, pp. 615-624

Abstract

A current model of growth factor-induced cell motility invokes integration of diverse biophysical processes required for cell motility, including dynamic formation and disruption of cell/substratum attachmentsalong with extension of membrane protrusions. To define how these biophysical events are actuated by biochemical signaling pathways, we investigate here whether epidermal growth factor (EGF) induces disruptionof focal adhesions in fibroblasts, We find that EGF treatment of NR6 fibroblasts presenting full-length WT EGF receptors (EGFR) reduces thefraction of cells presenting focal adhesions from similar to 60% to similar to 30% within 10 minutes. The dose dependency of focal adhesiondisassembly mirrors that for EGF-enhanced cell motility, being noted at 0.1 nM EGF. EGFR kinase activity is required as cells expressing two kinase-defective EGFR constructs retain their focal adhesions in thepresence of EGF. The short-term (30 minutes) disassembly of focal adhesions is reflected in decreased adhesiveness of EGF-treated cells to substratum. We further examine here known motility-associated pathwaysto determine whether these contribute to EGF-induced effects. We havepreviously demonstrated that phospholipase C gamma (PLC gamma) activation and mobilization of gelsolin from a plasma membrane-bound state are required for EGFR-mediated cell motility. In contrast, we find herethat short-term focal adhesion disassembly is induced by a signaling-restricted truncated EGFR (c'973) which fails to activate PLC gamma ormobilize gelsolin. The PLC inhibitor U73122 has no effect on this process, nor is the actin severing capacity of gelsolin required as EGF treatment reduces focal adhesions in gelsolin-devoid fibroblasts, further supporting the contention that focal adhesion disassembly is signaled by a pathway distinct from that involving PLC gamma. Because both WT and c'973 EGFR activate the erk MAP kinase pathway, we additionally explore here this signaling pathway, not previously associated with growth factor-induced cell motility. Levels of the MEK inhibitor PD98059that block EGF-induced mitogenesis and MAP kinase phosphorylation also abrogate EGF-induced focal adhesion disassembly and cell motility. In summary, we characterize for the first time the ability of EGFR kinase activity to directly stimulate focal adhesion disassembly and cell/substratum detachment, in relation to its ability to stimulate migration. Furthermore, we propose a model of EGF-induced motogenic cell responses in which the PLC gamma pathway stimulating cell motility is distinct from the MAP kinase-dependent signaling pathway leading to disassembly and reorganization of cell-substratum adhesion.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/07/20 alle ore 23:50:42