CHARACTERIZATION OF A RAT C-6 GLIOMA-SECRETED FOLLISTATIN-RELATED PROTEIN (FRP) - CLONING AND SEQUENCE OF THE HUMAN HOMOLOG

A protein was isolated from rat C-6 glioma-conditioned medium and was biochemically characterized. The heparin-binding protein has a native molecular mass of 55-75000 Da, a molecular mass of 40-48000 Da under denaturing conditions, and a pI of 5.0-6.0. Based on the determined partial amino acid sequences, the full length cDNA encoding the rat and human proteins were cloned. The cDNA sequences identified the isolated rat and human protein as the homologue of a recently reported mouse osteoblast-transforming-growth-factor-beta(1)-inducible protein, encoded by the TSC-36 gene [Shibanuma, M., Mashimo, J., Mita, A., Kuroki, T. and Nose, K. (1993) Eur. J. Biochem. 217, 13-19]. Analysis of the human, rat and mouse amino acid sequences indicates that these proteins are highly conserved (>92% sequence identity). Sequence similarities with follistatin and the follistatin-like domain of agrin are revealed. The relationship with follistatin and agrin points to possible common functions for the cloned follistatin-related proteins (FRP). The protein has no effect on the inhibitory action of transforming growth factor-beta(1), on CCl-64 cell growth.