The direct association of the multiple PDZ domain containing proteins (MUPP‐1) with the human c‐Kit C‐terminus is regulated by tyrosine kinase activity

Abstract
We have identified the multiple PDZ domain containing protein (MUPP‐1 or MPDZ) as a novel binding partner of the human c‐Kit. c‐Kit binds specifically to the 10th PDZ domain of MUPP‐1 via its C‐terminal sequence. Furthermore, a kinase negative‐mutant receptor interacted more strongly with MUPP‐1 than the wild‐type c‐Kit. Strikingly, a constitutively activated c‐Kit (D816V‐Kit) did not bind to MUPP‐1, although this oncogenic form retains the PDZ binding motif ‘HDDV’ at the C‐terminal end. Deletion of V967 of c‐Kit abolished binding to MUPP‐1 and drastically reduced its tyrosine kinase activity, suggesting that the structure of the C‐terminal tail of c‐Kit influences its enzymatic activity.