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Titolo:
Plasma membrane-associated pY397FAK is a marker of cytotrophoblast invasion in vivo and in vitro
Autore:
Ilic, D; Genbacev, O; Jin, F; Caceres, E; Almeida, EAC; Bellingard-Dubouchaud, V; Schaefer, EM; Damsky, CH; Fisher, SJ;
Indirizzi:
Univ Calif San Francisco, Dept Stomatol, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco,CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 rancisco,CA 94143 USA Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA Qual Controlled Biochem, Hopkington, MA USA Qual Controlled Biochem Hopkington MA USA ed Biochem, Hopkington, MA USA
Titolo Testata:
AMERICAN JOURNAL OF PATHOLOGY
fascicolo: 1, volume: 159, anno: 2001,
pagine: 93 - 108
SICI:
0002-9440(200107)159:1<93:PMPIAM>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
FOCAL ADHESION KINASE; JUN NH2-TERMINAL KINASE; CELL-MIGRATION; IN-VITRO; ENDOVASCULAR INVASION; TYROSINE KINASES; EARLY GESTATION; GROWTH-FACTOR; DIFFERENTIATION; INTEGRIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
55
Recensione:
Indirizzi per estratti:
Indirizzo: Fisher, SJ Univ Calif San Francisco, Dept Stomatol, 513 Parnassus,HSW-604,San Francisco, CA 94143 USA Univ Calif San Francisco 513 Parnassus,HSW-604San Francisco CA USA 94143
Citazione:
D. Ilic et al., "Plasma membrane-associated pY397FAK is a marker of cytotrophoblast invasion in vivo and in vitro", AM J PATH, 159(1), 2001, pp. 93-108

Abstract

During human pregnancy specialized placental cells of fetal origin, termedcytotrophoblasts, invade the uterus and its blood vessels. This tumor-likeprocess anchors the conceptus to the mother and diverts the now of uterineblood to the placenta. Previously, we showed that the expression of molecules with important functional roles, including a number of extracellular matrix integrin receptors, is precisely modulated during cytotrophoblast invasion in situ. Here we exploited this observation to study the role of the focal adhesion kinase (FAK), which transduces signals from the extracellularmatrix and recruits additional signaling proteins to focal adhesions. Immunolocalization studies on tissue sections showed that FAK is expressed by cytotrophoblasts in all stages of differentiation. Because extracellular matrix-induced integrin clustering results in FAK (auto)phosphorylation on tyrosine 397 (Y397FAK), we also localized this form of the molecule. Immunolocalization experiments detected Y397FAK in a subset of cytotrophoblasts nearthe surface of the uterine wall. To assess the functional relevance of this observation, we used an adenovirus strategy to inhibit cytotrophoblast expression of FAK as the cells differentiated along the invasive pathway in vitro. Compared to control cells transduced with a wild-type virus, cytotrophoblasts that expressed antisense FAK exhibited a striking reduction in their ability to invade an extracellular matrix substrate. When cytotrophoblast differentiation was compromised (hypoxia in vitro, preeclampsia in vivo),Y397FAK levels associated with the plasma membrane were strikingly lower, although total FAK levels did not change. Together our results suggest that(auto)phosphorylation of Y397 on FAK is a critical component of the signaling pathway that mediates cytotrophoblast migration/invasion.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/09/20 alle ore 20:01:05