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Titolo:
H-Ras is involved in the inside-out signaling pathway of interleukin-3-induced integrin activation
Autore:
Shibayama, H; Anzai, N; Braun, SE; Fukuda, S; Mantel, C; Broxmeyer, HE;
Indirizzi:
Indiana Univ, Sch Med, Walther Oncol Ctr, Indianapolis, IN 46202 USA Indiana Univ Indianapolis IN USA 46202 ol Ctr, Indianapolis, IN 46202 USA Indiana Univ, Sch Med, Dept Immunol Microbiol, Indianapolis, IN 46202 USA Indiana Univ Indianapolis IN USA 46202 robiol, Indianapolis, IN 46202 USA Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA Indiana Univ Indianapolis IN USA 46202 pt Med, Indianapolis, IN 46202 USA
Titolo Testata:
BLOOD
fascicolo: 5, volume: 93, anno: 1999,
pagine: 1540 - 1548
SICI:
0006-4971(19990301)93:5<1540:HIIITI>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
LATE ANTIGEN (VLA)-4; PHOSPHATIDYLINOSITOL 3-KINASE; CELL-ADHESION; R-RAS; KINASE; TRANSDUCTION; PROTEIN; INHIBITION; PROLIFERATION; FIBRONECTIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Broxmeyer, HE Indianaapolis,Sch Med, Walther Oncol Ctr, 1044 W Walnut St,Room 302, Indian Indiana Univ 1044 W Walnut St,Room 302 Indianapolis IN USA 46202
Citazione:
H. Shibayama et al., "H-Ras is involved in the inside-out signaling pathway of interleukin-3-induced integrin activation", BLOOD, 93(5), 1999, pp. 1540-1548

Abstract

The proto-oncogene product, p21(ras), has been implicated in the cellular mechanism of adhesion, although its precise role has been controversial. Numerous cytokines and growth-factors activate Ras, which is an important component of their growth-promoting signaling pathways. On the other hand, therole of Ras in cytokine-induced adhesion has not been elucidated. We therefore investigated the function of H-Ras in the inside-out signaling pathwayof interleukin-3 (IL-3)-induced integrin activation in the murine Baf3 cell line after transfection of cells with either constitutively active, dominant-negative, or wild-type H-Ras cDNAs. Adhesion of Baf3 cells to fibronectin was induced by IL-3 in a dose-dependent manner via very late antigen-4 (VLA-4; alpha 4 beta 1 integrins) and VLA-5 (alpha 5 beta 1 integrins) activation. On the other hand, IL-4 did not induce the adhesion of Baf3 cells tofibronectin, although IL-4 did stimulate the cell proliferation of Baf3 cells. Constitutively active H-Ras-transfected Baf3 cells adhered to fibronectin without IL-3 stimulation through VLA-4 and VLA-5, whereas dominant-negative H-Ras-transfected Baf3 cells showed significantly less adhesion induced by IL-3 compared with wild-type and constitutively active H-Ras-transfected Baf3 cells. Anti-beta 1 integrin antibody (clone; 9EG7), which is known to change integrin conformation and activate integrins, induced the adhesion of dominant-negative H-Ras-transfected Baf3 cells as much as the other types of H-Ras-transfected Baf3 cells. 8-Br-cAMP, Dibutyryl-cAMP, Ras-Raf-1 pathway inhibitors, and PD98059, a MAPK kinase inhibitor, suppressed proliferation and phosphorylation of MAPK detected by Western blotting with anti-phospho-MAPK antibody, but not adhesion of any type of H-Ras-transfected Baf3 cells, whereas U-73122, a phospholipase C (PLC) inhibitor, suppressed adhesion of these cells completely. These data indicate that H-Ras and PLC, but not Raf-1, MAPK kinase, or the MAPK pathway, are involved in the inside-out signaling pathway of IL-3-induced VLA-4 and VLA-5 activation in Baf3 cells. (C) 1999 by The American Society of Hematology.

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Documento generato il 04/06/20 alle ore 01:46:17