The Adenomatous Polyposis Coli-protein (APC) interacts with the protein tyrosine phosphatase PTP-BL via an alternatively spliced PDZ domain.
Mutations of the tumor suppressor protein APC (Adenomatous Polyposis Coli) are linked to familiar and sporadic human colon cancer. Here we describe a novel interaction between the APC protein and the protein tyrosine phosphatase PTP-BL carrying five PDZ protein-protein interaction domains. Exclusively, the second PDZ domain (PDZ2) of PTP-BL is binding to the extreme C-terminus of the APC protein, as determined by yeast two-hybrid studies. Using surface plasmon resonance analysis we established a dissociation constant (K(D)) of 8.1 x 10(-9) M. We find that a naturally occurring splice insertion of five amino acids (PDZ2b) abolishes its binding affinity to the APC protein. The in vivo interaction between PTP-BL and the APC protein was shown by coprecipitation experiments in transfected COS cells. Furthermore, in cultured epithelial Madine Carnine Kidney cells the subcellular colocalization was demonstrated for the nucleus and also for the tips of cellular extensions. The interaction of the APC protein with a protein tyrosine phosphatase may indirectly modulate the steady state levels of tyrosine phosphorylations of associated proteins, such as beta-catenin playing a major role in the regulation of cell division, migration and cell adhesion.
Erdmann
K S
KS
Department of Molecular Neurobiochemistry, Ruhr-University Bochum, Germany.
Kuhlmann
J
J
Lessmann
V
V
Herrmann
L
L
Eulenburg
V
V
Müller
O
O
Heumann
R
R
D025601:Adenomatous Polyposis Coli Protein; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger; D020349:Surface Plasmon Resonance; D015534:Trans-Activators; D014162:Transfection; D020798:Two-Hybrid System Techniques; D051176:beta Catenin
D025601:Adenomatous Polyposis Coli Protein; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D051176:beta Catenin; D017027:Protein Tyrosine Phosphatases