BASIC FIBROBLAST GROWTH-FACTOR INDUCES 3T3 FIBROBLASTS TO SYNTHESIZE AND SECRETE A CYCLOPHILIN-LIKE PROTEIN AND BETA-2-MICROGLOBULIN

When stimulated by fibroblast growth factor (FGF) BALB / c 3T3 cells synthesize and secrete elevated amounts of five proteins called the 'superinducible proteins', or SIPs. The expression of these proteins is greatly enhanced if the cells are treated with cycloheximide during induction. The 24 kDa protein (SIP24) has been purified and antiserum raised against it. This protein is N-glycosylated and probably structurally constrained by one or more intramolecular disulfide bonds. The amino acid sequences of three of four peptides show significant identity with cyclophilin, an abundant cytoplasmic protein believed to mediate the immunosuppressive effects of cyclosporin A. Several members of the cyclophilin family have been identified, and cDNA clones of two cyclophilin-like proteins with signal sequences have been reported. Here we show that at least one cyclophilin-like protein is secreted and that its expression is regulated by growth factors. The 12.5 kDa protein (SIP12.5) was found to be immunoprecipitated by an antiserum raised to human beta-2-microglobulin. This protein is strongly induced by interferon, which is a characteristic of the beta-2-microglobulin gene. Thus, FGF stimulates mouse embryo 3T3 cells to produce two proteins related to immune regulatory molecules. This may reflect an interaction between immune cells and nonimmune cells that occurs in vivo during processes such as wound healing when growth factors are released locally.