CROSS-LINKING OF FC-GAMMA RECEPTOR-I (FC-GAMMA-RI) AND RECEPTOR-II (FC-GAMMA-RII) ON MONOCYTIC CELLS ACTIVATES A SIGNAL-TRANSDUCTION PATHWAY COMMON TO BOTH FC-RECEPTORS THAT INVOLVES THE STIMULATION OF P72 SYKPROTEIN-TYROSINE KINASE

Stimulation of the human monocytic cell line THP-1 by cross-linking ei ther Fcgamma receptor I (FcgammaRI) or Fcgamma receptor II (FcgammaRII ) gave rise to the rapid phosphorylation of multiple intracellular pro teins. The pattern of proteins that were phosphorylated appeared to be identical. Analysis of these proteins by specific immunoprecipitation indicated that stimulation through either receptor did indeed give ri se to phosphorylation of the same set of proteins. These included: Fcg ammaRII, phospholipase C (PLC) gamma1, PLCgamma2, Vav, GAP, and a prot ein that co-precipitated with the Fcgamma receptors and migrated with a molecular weight of about 70,000. Co-cross-linking an F(ab')2 anti-C D45 monoclonal antibody together with monoclonal antibodies to either of the Fcgamma receptors inhibited phosphorylation of all these protei ns. Analysis of the tyrosine kinases in the cells revealed that both r eceptors stimulated the phosphorylation and activation of a kinase rec ognized by antibodies to Syk. Furthermore, the Syk kinase became assoc iated with the Fc-gammaRII following receptor cross-linking. These dat a indicate that although the two Fcgamma receptors have different cyto plasmic tails, they are coupled to the same signal transduction cascad e that is regulated by CD45 and involves the activation of Syk.