De novo expression of pp125(FAK) in human macrophages regulates CSK distribution and MAP kinase activation but does not affect focal contact structure

The protein tyrosine kinase pp125(FAK) (focal adhesion kinase, or FAK) is e xpressed by a variety of cell types and has been implicated in integrin-med iated signaling events. We explored the potential functions of FAK by expre ssing it de novo in a cell type lacking FAK. We showed previously that cult ured human macrophages lack FAK yet still have well-formed focal contacts. Adenovirus-mediated expression of FAK results in the appearance of FAK prot ein, which localizes to focal contacts and becomes tyrosine-phosphorylated without perturbing overall cell morphology or focal contacts. FAK associate s With CSK 48 h after infection and recruits it to focal contacts. Tyrosine phosphorylation of p130(cas) but not of paxillin is stimulated after FAK e xpression. The phosphorylation of p130(cas) is lost at 48 h in parallel wit h CSK accumulation in focal contacts. The ERK2 form of MAP kinase is simila rly activated at 12-24 h, but it also returns to low levels at 48 h. These findings demonstrate that FAK can be reconstituted to focal contacts in cel ls that lack it without affecting cell morphology or focal contact structur e. FAK can regulate the distribution and activities of elements of the MAP kinase signaling pathway. J Cell Physiol 178:164-172, 1999. Published 1:999 Wiley-Liss, Inc.dagger.