Integrin-mediated ras-extracellular regulated kinase (ERK) signaling regulates interferon gamma production in human natural killer cells

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

doi:10.1084/jem.188.7.1267

Integrin-mediated ras-extracellular regulated kinase (ERK) signaling regulates interferon gamma production in human natural killer cells

J Exp Med. 1998 Oct 5;188(7):1267-75. doi: 10.1084/jem.188.7.1267.

Authors

F Mainiero¹, A Gismondi, A Soriani, M Cippitelli, G Palmieri, J Jacobelli, M Piccoli, L Frati, A Santoni

Affiliation

¹ Department of Experimental Medicine and Pathology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome "La Sapienza", 00161 Rome, Italy.

Abstract

Recent evidence indicates that integrin engagement results in the activation of biochemical signaling events important for regulating different cell functions, such as migration, adhesion, proliferation, differentiation, apoptosis, and specific gene expression. Here, we report that beta1 integrin ligation on human natural killer (NK) cells results in the activation of Ras/mitogen-activated protein kinase pathways. Formation of Shc-growth factor receptor-bound protein 2 (Grb2) and Shc-proline-rich tyrosine kinase 2-Grb2 complexes are the receptor-proximal events accompanying the beta1 integrin-mediated Ras activation. In addition, we demonstrate that ligation of beta1 integrins results in the stimulation of interferon gamma (IFN-gamma) production, which is under the control of extracellular signal-regulated kinase 2 activation. Overall, our data indicate that beta1 integrins, by delivering signals capable of triggering IFN-gamma production, may function as NK-activating receptors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing*
Adaptor Proteins, Vesicular Transport*
Animals
Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
Cells, Cultured
Cross-Linking Reagents
Enzyme Activation
GRB2 Adaptor Protein
Humans
Integrin beta1 / metabolism*
Interferon-gamma / biosynthesis*
Killer Cells, Natural / metabolism*
Mice
Mitogen-Activated Protein Kinase 1
Phosphorylation
Proteins / metabolism
Shc Signaling Adaptor Proteins
Signal Transduction*
Src Homology 2 Domain-Containing, Transforming Protein 1
Tyrosine / metabolism

Substances

Adaptor Proteins, Signal Transducing
Adaptor Proteins, Vesicular Transport
Cross-Linking Reagents
GRB2 Adaptor Protein
GRB2 protein, human
Grb2 protein, mouse
Integrin beta1
Proteins
SHC1 protein, human
Shc Signaling Adaptor Proteins
Shc1 protein, mouse
Src Homology 2 Domain-Containing, Transforming Protein 1
Tyrosine
Interferon-gamma
Calcium-Calmodulin-Dependent Protein Kinases
Mitogen-Activated Protein Kinase 1