Identification of a Gene Family Regulated by Transforming Growth Factor-β

Abstract

We have identified two related genes whose mRNAs are increased after treatment with transforming growth factor-β (TGF-β1). Mouse AKR-2B cells were treated with TGF-β1 in the presence of cyclohexamide and a cDNA library was subjected to differential screening. Several TGF-β-induced genes (βIG) were isolated and two of these, βIG-M1 and βIG-M2, were characterized. βIG-M1 and βIG-M2 RNAs were significantly increased after TGF-β1 treatment and both were superinduced in the presence of cyclohexamide. cDNA sequence analysis of βIG-M1 showed that it encoded a 379-amino-acid protein which was 81% homologous to CEF-10, a v-src and TPA-inducible gene, and identical to cyr61, a gene induced by serum in growth-arrested BALB-3T3 cells. cDNA sequence analysis of βIG-M2 showed that it encoded a 348-amino-acid protein that was 50% homologous to βIG-M1. Thirty-eight cysteine residues are conserved between βIG-M1 and βIG-M2, which are clustered at the amino and carboxy ends: The middle regions of the two proteins are cysteine free and display the highest degree of nonhomology. Both proteins contain an amino-terminal cysteine-rich motif common to insulin-like growth factor binding proteins and a carboxy-terminal domain with strong homology to a motif found near the carboxy-terminal of the malarial circumsporozoite protein which may be involved in cell adhesion. The regulation of mRNA encoding these proteins by TGF-β1 suggests that they may be involved in mediating some of the pleiotropic effects of this multipotent modulator of cell growth and differentiation.