Isolation and characterization of a siderophore-like growth factor from mutants of SV40-transformed cells adapted to picolinic acid.

We have isolated mutants of SV40-transformed BALB/3T3 cells adapted to grow in picolinic acid. A line of cells, derived from the mutant cells, that multiplies in the absence of serum has also been characterized. From ultrafiltrates of medium conditioned by contact with these cell lines, we have identified and partially purified a highly specific iron-binding ligand termed siderophore-like growth factor (SGF). Experiments have indicated that the factor is a peptide(s) of approximately 1600 daltons. In nanogram amounts, SGF solubilizes and binds Fe 3+ in vitro and stimulates the uptake of Fe 3+ in vivo. The Fe 3+ uptake preceded the stimulation of DNA synthesis induced by the factor in the mutant cell lines. The factor could not be separated into Fe 3+ binding and DNA synthetic activity, suggesting that the early iron uptake is an integral component of the proliferative response. These data support the hypothesis that SGF is representative of a family of mammalian siderophores which may have an important role in cell proliferation.