Coupling of β1 integrin to RAS-MAP kinase pathways controls IFNγ mRNA expression in human NK cells

F. Mainiero, A. Gismondi, M. Cippitelli, G. Palmieri, A. Soriani, J. Jacobelli, M. Piccoli, L. Frati, A. Santoni

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In this study we analyzed whether β1 integrin ligation on human NK cells may result in the stimulation of the Ras/MAPK signaling pathways via Shc and thereby modulate the expression of IFNγ gene. Our data demonstrate that upon β1 integrin ligation on human NK cells, both p46 and p52 forms of Shc were tyrosine phosphorylated. Shc immune-precipitates from lysates of β1-stimulated NK cells contained Grb2 and a 145 kD tyrosine phosphoprotein. We also show that p21ras and MAP kinases Erk and Jnk are activated by β1 cross-linking. While accumulation of GTP-bound Ras was maximal at 5 minute and occurred with a kinetics similar to Shc tyrosine phosphorylation and Grb2 association to Shc, Erk and Jnk activation was maximal at 20 minutes. In addition we present evidence that β1 integrin ligation enhances IFNγ mRNA expression which was maximal at 30 min and declined at 3 h after stimulation. β1 integrin-stimulated IFNγ mRNA expression was partially decreased (50-60%) by the synthetic inhibitor PD 098059, which has been reported to specifically prevent MEK-1 activation. These findings indicate that ligation of β1 integrins on human NK cells results in the stimulation of IFNγ mRNA expression, which involves Erk2 activation.

Original languageEnglish
JournalFASEB Journal
Issue number5
Publication statusPublished - Mar 20 1998

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology


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