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Titolo:
Dual role of H-Ras in regulation of lymphocyte function antigen-1 activityby stromal cell-derived factor-1 alpha: Implications for leukocyte transmigration
Autore:
Weber, KSC; Ostermann, G; Zernecke, A; Schroder, A; Klickstein, LB; Weber, C;
Indirizzi:
Univ Munich, Inst Prevent & Cardiovasc Dis, D-80336 Munich, Germany Univ Munich Munich Germany D-80336 rdiovasc Dis, D-80336 Munich, Germany Univ Hosp, Dept Cardiovasc Mol Med, D-52074 Aachen, Germany Univ Hosp Aachen Germany D-52074 iovasc Mol Med, D-52074 Aachen, Germany Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol & Immunol, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 heumatol & Immunol, Boston, MA 02115 USA
Titolo Testata:
MOLECULAR BIOLOGY OF THE CELL
fascicolo: 10, volume: 12, anno: 2001,
pagine: 3074 - 3086
SICI:
1059-1524(200110)12:10<3074:DROHIR>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
SIGNAL-TRANSDUCTION PATHWAYS; INTEGRIN-MEDIATED ADHESION; PHOSPHATIDYLINOSITOL 3-KINASE; LIGAND-BINDING; TRANSENDOTHELIAL CHEMOTAXIS; T-LYMPHOCYTES; PHOSPHOINOSITIDE 3-KINASE; DIFFERENTIAL REGULATION; ACTIN CYTOSKELETON; KINASE PATHWAY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: Weber, C Univ Munich, Inst Prevent & Cardiovasc Dis, D-80336 Munich, Germany Univ Munich Munich Germany D-80336 Dis, D-80336 Munich, Germany
Citazione:
K.S.C. Weber et al., "Dual role of H-Ras in regulation of lymphocyte function antigen-1 activityby stromal cell-derived factor-1 alpha: Implications for leukocyte transmigration", MOL BIOL CE, 12(10), 2001, pp. 3074-3086

Abstract

We investigated the role of H-Ras in chemokine-induced integrin regulationin leukocytes. Stimulation of jurkat T cells with the CXC chemokine stromal cell-derived factor-1 alpha (SDF-1 alpha) resulted in a rapid increase inthe phosphorylation, i.e., activation of extracellular signal receptor-activated kinase (ERK) but not c-jun NH2-terminal kinase or p38 kinase, and phosphorylation of Akt, reflecting phosphatidylinositol 3-kinase (PI3-K) activation. Phosphorylation of ERK in Jurkat cells was enhanced and attenuated by expression of dominant active (D12) or inactive (N17) forms of H-Ras, respectively, while N17 H-Ras abrogated SDF-1 alpha -induced Akt phosphorylation. SDF-1 alpha triggered a transient regulation of adhesion to intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 mediated by lymphocyte function antigen-1 (LFA-1) and very late antigen-4 (VLA-4), respectively, and a rapid increase in LFA-1 binding to soluble ICAM-1.Ig, which was inhibited by D12 but not N17 H-Ras. Both D12 and N17 H-Ras abrogated the regulation of LFA-1 but not VLA-4 avidity, and impaired LFA-1-mediated transendothelial chemotaxis but not VLA-4-dependent transmigration induced by SDF-1a. Analysis of the mutant Jurkat J19 clone revealed LFA-1 with constitutively high affinity and reduced ERK phosphorylation, which werepartially restored by expression of active H-Ras. Inhibition of PI3-K blocked the up-regulation of Jurkat cell adhesion to ICAM-1 by SDF-1 alpha, whereas inhibition of mitogen-activated protein kinase kinase impaired the subsequent down-regulation and blocking both pathways abrogated LFA-1 regulation. Our data suggest that inhibition of initial PI3-K activation by inactive H-Ras or sustained activation of an inhibitory ERK pathway by active H-Ras prevail to abolish LFA-1 regulation and transendothelial migration induced by SDF-1a in leukocytes, establishing a complex and bimodal involvement of H-Ras.

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Documento generato il 12/07/20 alle ore 12:46:29