ERBIN: a basolateral PDZ protein that interacts with the mammalian ERBB2/HER2 receptor

The ERBB receptors have a crucial role in morphogenesis and oncogenesis. We have identified a new PDZ protein we named ERBIN (ERBB2 interacting protei n) that acts as an adaptor for the receptor ERBB2/HER2 in epithelia. ERBIN contains 16 leucine-rich repeats (LRRs) in its amino terminus and a PDZ (PS D-95/DLG/ZO-1) domain at its carboxy terminus, and belongs to a new PDZ pro tein family. The PDZ domain directly and specifically interacts with ERBB2/ HER2. ERBIN and ERBB2/HER2 colocalize to the lateral membrane of human int estinal epithelial cells. The ERBIN-binding site in ERBB2/HER2 has a critic al role in restricting this receptor to the basolateral membrane of epithel ial cells, as mutation of the ERBIN-binding site leads to the mislocalizati on of the receptor in these cells. We suggest that ERBIN acts in the locali zation and signalling of ERBB2/HER2 in epithelia.