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Titolo:
Cross-talk between alpha(4)beta(1)/alpha(5)beta(1) and c-Kit results in opposing effect on growth and survival of hematopoietic cells via the activation of focal adhesion kinase, mitogen-activated protein kinase, and Akt signaling pathways
Autore:
Kapur, R; Cooper, R; Zhang, L; Williams, DA;
Indirizzi:
Indiana Univ, Sch Med,James Whitcomb Riley Hosp Children, Howard Hughes Med Inst,Dept Pediat, Herman B Wells Ctr Pediat Res,Sect Pediat Hematol, Indianapolis, IN 46202 USA Indiana Univ Indianapolis IN USA 46202 ematol, Indianapolis, IN 46202 USA
Titolo Testata:
BLOOD
fascicolo: 7, volume: 97, anno: 2001,
pagine: 1975 - 1981
SICI:
0006-4971(20010401)97:7<1975:CBAACR>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
MURINE ERYTHROLEUKEMIA-CELLS; HEPARIN-BINDING DOMAIN; BONE-MARROW STROMA; PROGENITOR CELLS; ERYTHROID-DIFFERENTIATION; EXTRACELLULAR-MATRIX; STEEL FACTOR; MAST-CELLS; IN-VIVO; INTEGRIN ALPHA-4-BETA-1;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
69
Recensione:
Indirizzi per estratti:
Indirizzo: Kapur, R Indiana Univ, Sch Med,James Whitcomb Riley Hosp Children, Howard Hughes Med Inst,Dept Pediat, Herman B Wells Ctr Pediat Res,Sect Pediat Hematol, CancRes Bldg,1044 W Walnut St,Rm 425, Indianapolis, IN 46202 USA Indiana Univ Canc Res Bldg,1044 W Walnut St,Rm 425 Indianapolis IN USA 46202
Citazione:
R. Kapur et al., "Cross-talk between alpha(4)beta(1)/alpha(5)beta(1) and c-Kit results in opposing effect on growth and survival of hematopoietic cells via the activation of focal adhesion kinase, mitogen-activated protein kinase, and Akt signaling pathways", BLOOD, 97(7), 2001, pp. 1975-1981

Abstract

Erythroid progenitor cells (EPCs) are deficient in mice lacking either theligand stem cell factor (SCF), its receptor c-Kit, or beta (1)-integrins, In nonhematopoietic cells, integrins and receptor tyrosine kinases can collaborate to modulate cellular functions, providing evidence for cross-talk between signals emerging from these cell surface molecules. Using specific recombinant fibronectin peptides that contain the binding site for the integrin alpha (4)beta (1) (FN-H296) or alpha (5)beta (1) (FN-CH271) Or both alpha (4)beta (1) and alpha (5)beta (1) (FN-CH296), this study investigated the effect of adhesion alone, or in combination with activation of c-Kit, on functional and biochemical outcomes in an EPC line, G1E-ER2, and primary EPCs, G1E-ER2 cells and primary EPCs cultured on FN-CH271 in the presence of c-KR activation led to a significant increase in proliferation in comparison with cells grown on FN-H296 or FN-CH296, G1E-ER2 cells cultured on FN-H296 or FN-CH296 resulted in significant cell death in comparison to cells grown on FN-CH271, Activation of c-Kit enhanced the survival of G1E-ER2 cells grown on FN-H296 or FN-CH296; however, the rescue was only partial. The reduced survival of G1E-ER2 cells on FN-H296 correlated with reduced activation of Akt and expression of Bcl-2 and Bcl-x(L), whereas increase in proliferation on FN-CH271 correlated with significantly enhanced and sustained activation of focal adhesion kinase (FAK) and extracellular-regulated kinase (ERK) pathways. These data demonstrate that adhesion-induced signals emanating from ligation of alpha (4)beta (1) and alpha (5)beta (1) result in distinct biologic outcomes, including death via alpha (4)beta (1) and survival/proliferation via alpha (5)beta (1) (Blood, 2001;97:1975-1981) (C) 2001 by The American Society of Hematology.

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Documento generato il 05/12/20 alle ore 20:14:55