A gene sequence (TSC-22) that is induced by transforming growth factor (TGF) beta 1 was isolated by differential screening of a lambda gt10 cDNA library constructed from poly(A)+ RNA of mouse osteoblastic cells treated with TGF-beta 1 for 2 h. TSC-22 gene expression was transcriptionally activated by TGF-beta 1. It was also induced by phorbol 12-myristate 13-acetate, serum, cholera toxin, or dexamethasone, but not appreciably by epidermal growth factor. Its induction was rapid and transient, reaching a peak 2 h after TGF-beta 1 treatment, and was resistant to cycloheximide like that of c-jun. The nucleotide sequences of TSC-22 cDNA showed no homology with any known gene sequence. The open reading frame and in vitro translation product indicated that the gene encodes a polypeptide of 143 amino acids with a molecular mass of 18 kDa that contains a putative leucine zipper structure. Polyclonal antibody was raised against TSC-22 protein expressed in Escherichia coli cells, and the antibody detected a 18-kDa protein in both the cytoplasmic and nuclear fractions of [35S]Met-labeled cells. These results indicate that the TSC-22 gene is a new member of the family of early response genes, and encodes a small polypeptide that is a putative transcriptional regulator.