Involvement of pp125(FAK) and p60(SRC) in the signaling through Fc gamma RII-Fc gamma RIII in murine macrophages

Cross-linking the FcyRs can activate a wide variety of biological responses in macrophages. Receptor stimulation induces activation of protein tyrosin e kinase cascades that result in phagocytosis. a process known to involve c ytoskeletal rearrangements. Therefore, an involvement of non-receptor tyros ine kinases such as pp125(FAK), in FcyR signaling is likely. Using the muri ne macrophage cell line J774. we demonstrate that Fcy7RII-RIII cross-linkin g induces a time- and dose-dependent increase in tyrosine phosphorylation o f the focal adhesion kinase pp125(FAK) that correlates with an increase in its catalytic activity. Interestingly enough. pp125(FAK) activation results in its association both to the FcyRII-III and to p60(Src). The results pre sented here define a novel-signaling pathway likely to be important in low affinity FcyRII-III mediated phagocytosis. (C) 2001 Elsevier Science B.V. A ll rights reserved.