Stimulation of protein tyrosine phosphorylation by interaction of NK cells with fibronectin via α4β1 and α5β

Angela Gismondi, Michele Milella, Gabriella Palmieri, Mario Piccoli, Luigi Frati, Angela Santoni

Research output: Contribution to journalArticle


Recent evidence indicates that integrins do transduce signals that are involved in the regulation of a number of cellular processes. We have shown previously that human NK cells express α4β1 and α5β1 integrins, which mediate their adhesion to fibronectin (FN). Here we investigate whether cross-linking of β1 FN receptors on human NK cells stimulates tyrosine kinase activation. Our results indicate that cross-linking of β1 integrins on NK cells, either freshly isolated from PBL or generated from 10-day coculture of nonadherent PBMC with an irradiated EBV+ lymphoblastoid B cell line (long-term activated NK cells), altered the tyrosine phosphorylation pattern. In particular, we found stimulation of tyrosine phosphorylation of two proteins migrating with an apparent mass of 105 and 115 kDa, which was not observed after CD16 engagement. Phosphorylation of pp105-115 was already observed at 1 min, raised maximal values at 3 to 5 min, and persisted until 20 min after stimulation. Tyrosine phosphorylation of pp105-115 was also observed upon engagement of α4β1 and α5β1 FN receptors either with mAb directed against the a subunits or after NK cell adhesion to FN or its 120-and 40-kDa fragments. Pretreatment of NK cells with the tyrosine kinase inhibitor herbimycin A resulted in marked decrease of phosphorylation stimulated through α4β1 and α5β1 integrins, indicating that ligation of FN receptors on NK cells activates tyrosine kinase(s). Overall our results suggest that β1 integrins on NK cells play a major role as signaling molecules in the regulation of NK cell functions.

Original languageEnglish
Pages (from-to)3128-3137
Number of pages10
JournalJournal of Immunology
Issue number7
Publication statusPublished - 1995

ASJC Scopus subject areas

  • Immunology

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