INTERACTION OF TRANSFORMING GROWTH-FACTOR-BETA RECEPTORS WITH APOLIPOPROTEIN J CLUSTERIN/

Proteins mediating the transmission of the signal from an activated tr ansforming growth factor beta (TGF beta) receptor complex have not bee n 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. Apo J interacts with both the type I (RT) and type II (RII) TGF beta recep tors but does not interact with the epidermal growth factor (EGF) rece ptor. The interaction between RII and apoJ occurs through the C-termin al 127 amino acids of RII. Deletion of this region, which contains the kinase insert 2 domain, abrogates binding to apoJ. The binding of apo J to either the RI and the RII receptors is direct, not requiring othe r 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 [S-35]methionine-labeled cellular lysates, suggesti ng that this form of the protein may play some role in TGF beta signal ing or TGF beta receptor processing.