Interaction of Transforming Growth Factor β Receptors with Apolipoprotein J/Clusterin

Abstract

Proteins mediating the transmission of the signal from an activated transforming growth factor beta (TGF beta) receptor complex have not been identified. Using a yeast interaction screen to search for proteins that associate with the type II TGF beta receptor (RII), we isolated a protein which was identical to apolipoprotein J (apoJ)/clusterin. ApoJ interacts with both the type I (RI) and type II (RII) TGF beta receptors but does not interact with the epidermal growth factor (EGF) receptor. The interaction between RII and apoJ occurs through the C-terminal 127 amino acids of RII. Deletion of this region, which contains the kinase insert 2 domain, abrogates binding to apoJ. The binding of apoJ to either the RI and the RII receptors is direct, not requiring other proteins, and is not specific for the alpha or beta subunit of apoJ since both subunits are effective in competing for binding. RI and RII fusion proteins are capable of precipitating the 60 kDa intracellular form of apoJ from [35S]methionine-labeled cellular lysates, suggesting that this form of the protein may play some role in TGF beta signaling or TGF beta receptor processing.