EARLY SIGNAL-TRANSDUCTION BY THE RECEPTOR TO THE CHEMOKINE MONOCYTE CHEMOTACTIC PROTEIN-1 IN A MURINE T-CELL HYBRID

Members of the C-C family of chemotactic cytokines promote chemotaxis and adhesion of leukocytes, In this study, we have identified a murine T cell hybrid that expresses receptors to the chemotactic cytokine mo nocyte chemotactic protein-1 (MCP-1), This cell line was used to exami ne MCP-1 receptor-mediated signal transduction events in a homologous system in the absence of interference with other receptors. Our result s show that in the 3B4 M1.9 T cell hybrid, MCP-1 receptors mediate int racellular calcium mobilization and extracellular calcium import witho ut detectable increases in total water-soluble inositol phosphates. In addition, MCP-1 regulates the tyrosine phosphorylation of specific su bstrates at 42 and 44 kDa and induces mobility shift of p42/44 mitogen -activated protein kinases, MCP-l-mediated calcium responses, tyrosine phosphorylation, and the electrophoretic mobility shift of p42/44 mit ogen-activated protein kinases can be inhibited by pretreatment of cel ls with pertussis toxin, indicating a role for G(i)-like G proteins in coupling the MCP-1R to signal transduction.