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 phosphat ase PTP-BL carrying five PDZ protein-protein interaction domains. Exclusive ly, the second PDZ domain (PDZ2) of PTP-BL is binding to the extreme C-term inus of the APC protein, as determined by yeast two-hybrid studies. Using s urface 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 prote in. The in vivo interaction between PTP-BL and the APC protein was shown by coprecipitation experiments in transfected COS cells. Furthermore, in cult ured epithelial Madine Carnine Kidney cells the subcellular colocalization was demonstrated for the nucleus and also for the tips of cellular extensio ns, The interaction of the APC protein with a protein tyrosine phosphatase may indirectly modulate the steady state levels of tyrosine phosphorylation s of associated proteins, such as beta-catenin playing a major role in the regulation of cell division, migration and cell adhesion.