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.
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.
Mancini
A
A
Institut für Biochemie, -OE 4310-, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30623 Hannover, Germany.
Koch
A
A
Stefan
M
M
Niemann
H
H
Tamura
T
T
D000595:Amino Acid Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017384:Sequence Deletion
D002352:Carrier Proteins; C111442:MPDZ protein, human; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit