Structural requirements of Syk kinase for Fc gamma receptor-phagocytosis

The tyrosine kinase Syk plays a critical role in the phagocytic pathway med iated by Fc gamma receptors (Fc gamma R), In transfected COS1 cells co-expr ession of Syk enhances Fc gamma R mediated phagocytosis, The other member o f the Syk kinase family, the highly homologous tyrosine kinase Zap70, also plays a role in signaling by immunoglobulin gene family receptors, but does not increase the phagocytic efficiency of Fc gamma Rs, The homologous tand em SH2 and kinase domains of Syk and Zap70 are separated by a nonhomologous region referred to as the unique domain. Zap70's inability to enhance phag ocytosis was not due to unique domain tyrosine 292, previously implicated i n negative regulation of Zap70 function. We determined the regions of Syk i mportant for its interaction with the phagocytic pathway, An intact kinase domain was required for Syk's effect on phagocytosis, Furthermore, the Syk variant SykB, lacking 23 amino acids in the unique region, signaled for pha gocytosis as efficiently as did Syk, We then constructed exchange chimeras between Syk and Zap70 and determined the contributions of the SH2, unique a nd kinase domains to phagocytic signaling. Our data suggest that the Syk ki nase domain, which has high intrinsic kinase activity, is important for fac ilitating phagocytic signaling by Fc gamma RI and Fc gamma RIIIA, (C) 1999 International Society for Experimental Hematology. Published by Elsevier Sc ience Inc.