INTEGRIN-MEDIATED RAS-EXTRACELLULAR REGULATED KINASE (ERK) SIGNALING REGULATES INTERFERON-GAMMA PRODUCTION IN HUMAN NATURAL-KILLER-CELLS

Recent evidence indicates that integrin engagement results in the acti vation of biochemical signaling events important for regulating differ ent cell functions, such as migration, adhesion, proliferation, differ entiation, apoptosis, and specific gene expression. Here, we report th at beta 1 integrin ligation on human natural killer (NK) cells results in the activation of Ras/mitogen-activated protein kinase pathways. F ormation of She-growth factor receptor-bound protein 2 (Grb2) and Shc- proline-rich tyrosine kinase 2-Grb2 complexes are the receptor-proxima l events accompanying the beta 1 integrin-mediated Ras activation. In addition, we demonstrate that ligation of beta 1 integrins results in the stimulation of interferon gamma (IFN-gamma) production, which is u nder the control of extracellular signal-regulated kinase 2 activation . Overall, our data indicate that beta 1 integrins, by delivering sign als capable of triggering IFN-gamma production, may function as NK-act ivating receptors.