Mancini A, Koch A, Stefan M, Niemann H, Tamura T
Institut für Biochemie, -OE 4310-, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30623 Hannover, Germany.
FEBS Lett. 2000 Sep 29;482(1-2):54-8. doi: 10.1016/s0014-5793(00)02036-6.
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.
我们已确定含多个PDZ结构域的蛋白（MUPP-1或MPDZ）是人类c-Kit的一种新型结合伴侣。c-Kit通过其C端序列与MUPP-1的第10个PDZ结构域特异性结合。此外，激酶阴性突变体受体与MUPP-1的相互作用比野生型c-Kit更强。引人注目的是，组成型激活的c-Kit（D816V-Kit）不与MUPP-1结合，尽管这种致癌形式在C末端保留了PDZ结合基序“HDDV”。c-Kit的V967缺失消除了与MUPP-1的结合，并大幅降低其酪氨酸激酶活性，这表明c-Kit C末端尾巴的结构影响其酶活性。
