A. Gismondi et al., STIMULATION OF PROTEIN-TYROSINE PHOSPHORYLATION BY INTERACTION OF NK CELLS WITH FIBRONECTIN VIA ALPHA-4-BETA-1 AND ALPHA-5-BETA-1, The Journal of immunology, 154(7), 1995, pp. 3128-3137
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 alpha 4 beta 1 and alpha
5 beta 1 integrins, which mediate their adhesion to fibronectin (FN).
Here we investigate whether cross-linking of beta 1 FN receptors on h
uman NK cells stimulates tyrosine kinase activation. Our results indic
ate that cross-linking of beta 1 integrins on NK cells, either freshly
isolated from PBL or generated from 10-day coculture of nonadherent P
BMC with an irradiated EBV(+) lymphoblastoid B cell line (long-term ac
tivated NK cells), altered the tyrosine phosphorylation pattern. In pa
rticular, we found stimulation of tyrosine phosphorylation of two prot
eins migrating with an apparent mass of 105 and 115 kDa, which was not
observed after CD16 engagement. Phosphorylation of pp105-115 was alre
ady observed at 1 min, raised maximal values at 3 to 5 min, and persis
ted until 20 min after stimulation. Tyrosine phosphorylation of pp105-
115 was also observed upon engagement of alpha 4 beta 1 and alpha 5 be
ta 1 FN receptors either with mAb directed against the alpha subunits
or after NK cell adhesion to FN or its 120- and 40-kDa fragments. Pret
reatment of NK cells with the tyrosine kinase inhibitor herbimycin A r
esulted in marked decrease of phosphorylation stimulated through alpha
4 beta 1 and alpha 5 beta 1 integrins, indicating that ligation of FN
receptors on NK cells activates tyrosine kinase(s). Overall our resul
ts suggest that beta 1 integrins on NK cells play a major role as sign
aling molecules in the regulation of NK cell functions.