The carboxyl-terminal region of biliary glycoprotein controls its tyrosine phosphorylation and association with protein-tyrosine phosphatases SHP-1 and SHP-2 in epithelial cells.

摘要: Biliary glycoprotein (Bgp, C-CAM, or CD66a) is an immunoglobulin-like cell adhesion molecule and functions as a tumor suppressor protein. We have previously shown that the Bgp1 isoform responsible for inhibition of colonic, liver, prostate, breast growth contains within its cytoplasmic domain two tyrosine residues positioned in immunoreceptor tyrosine-based motif (ITIM) consensus sequences. Moreover, we determined these residues, upon phosphorylation, associate with protein-tyrosine phosphatase SHP-1. In this report, further evaluated structural bases association Tyr phosphatases. First, demonstrate also associates SHP-2 phosphatase, but not unrelated PTP-PEST. Association involves ITIM sequences, Val at position +3 relative to second (Tyr-515), N-terminal SH2 domain. addition, our results indicate +4, +5, +6 Tyr-515 play significant role interactions, their deletion reduced phosphorylation SHP-1 by much 80%. Together, both interact via ITIM-like Furthermore, they reveal C-terminal amino acids are critical interactions.