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
| Autor: | Nicole Beauchemin, Maria Huber, Philippe Grondin, Tilo Kunath, Caroline Houde, Luisa Izzi, André Veillette |
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| Rok vydání: | 1999 |
| Předmět: |
Gene isoform
Cytoplasm SH2 Domain-Containing Protein Tyrosine Phosphatases animal structures Molecular Sequence Data Phosphatase Protein Tyrosine Phosphatase Non-Receptor Type 11 chemical and pharmacologic phenomena Protein tyrosine phosphatase Biology SH2 domain Biochemistry Cell Line Mice chemistry.chemical_compound Cytosol Antigens CD Tumor Cells Cultured Animals Humans Amino Acid Sequence Phosphorylation Tyrosine Molecular Biology DNA Primers Glycoproteins Base Sequence Cell growth Protein Tyrosine Phosphatase Non-Receptor Type 6 Intracellular Signaling Peptides and Proteins Epithelial Cells hemic and immune systems Tyrosine phosphorylation Cell Biology Molecular biology chemistry Protein Tyrosine Phosphatases Cell Adhesion Molecules |
| Zdroj: | Journal of Biological Chemistry. 274:335-344 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.274.1.335 |
| Popis: | 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, and breast tumor cell growth contains within its cytoplasmic domain two tyrosine residues positioned in immunoreceptor tyrosine-based inhibition motif (ITIM) consensus sequences. Moreover, we determined that these residues, upon phosphorylation, associate with the protein-tyrosine phosphatase SHP-1. In this report, we have further evaluated the structural bases of the association of Bgp1 with Tyr phosphatases. First, we demonstrate that Bgp1 also associates with the SHP-2 Tyr phosphatase, but not with an unrelated Tyr phosphatase, PTP-PEST. Association of Bgp1 and SHP-2 involves the Tyr residues within the Bgp1 ITIM sequences, Val at position +3 relative to the second Tyr (Tyr-515), and the SHP-2 N-terminal SH2 domain. In addition, our results indicate that residues +4, +5, and +6 relative to Tyr-515 in the Bgp1 cytoplasmic domain play a significant role in these interactions, as their deletion reduced Bgp1 Tyr phosphorylation and association with SHP-1 and SHP-2 by as much as 80%. Together, these results indicate that both SHP-1 and SHP-2 interact with the Bgp1 cytoplasmic domain via ITIM-like sequences. Furthermore, they reveal that the C-terminal amino acids of Bgp1 are critical for these interactions. |
| Databáze: | OpenAIRE |
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