Recruitment of the protein-tyrosine phosphatase SHP-2 to the C-terminal tyrosine of the prolactin receptor and to the adaptor protein Gab2.
The protein-tyrosine phosphatase SHP-2 modulates signaling events through receptor tyrosine kinases and cytokine receptors including the receptor for prolactin (PRLR). Here we investigated mechanisms of SHP-2 recruitment within the PRLR signaling complex. Using SHP-2 and PRLR immunoprecipitation studies in 293 cells and in the mouse mammary epithelial cell line HC11, ... we found that SHP-2 co-immunoprecipitates with the PRLR and that the C-terminal tyrosine of the PRLR plays a regulatory role in both the tyrosine phosphorylation and the recruitment of SHP-2. Our results further indicate that SHP-2 association to the PRLR occurs via the C-terminal SH2 domain of the phosphatase. In addition, we determined that the newly identified adaptor protein Gab2, but not Gab1, is specifically tyrosine phosphorylated and is able to recruit SHP-2 and phosphatidyinositol 3-kinase in response to PRLR activation. Together, these studies suggest the presence of dual recruitment sites for SHP-2; the first is to the C-terminal tyrosine of the PRLR and the second is to the adaptor protein Gab2.
Mesh Terms:
1-Phosphatidylinositol 3-Kinase, Adaptor Proteins, Signal Transducing, Animals, Binding Sites, Blotting, Western, Breast, Cell Line, Epithelium, Humans, Intracellular Signaling Peptides and Proteins, Mice, Phosphoproteins, Phosphorylation, Plasmids, Precipitin Tests, Prolactin, Protein Binding, Protein Structure, Tertiary, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, Receptors, Prolactin, SH2 Domain-Containing Protein Tyrosine Phosphatases, Signal Transduction, Time Factors, Transfection, Tyrosine
1-Phosphatidylinositol 3-Kinase, Adaptor Proteins, Signal Transducing, Animals, Binding Sites, Blotting, Western, Breast, Cell Line, Epithelium, Humans, Intracellular Signaling Peptides and Proteins, Mice, Phosphoproteins, Phosphorylation, Plasmids, Precipitin Tests, Prolactin, Protein Binding, Protein Structure, Tertiary, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, Receptors, Prolactin, SH2 Domain-Containing Protein Tyrosine Phosphatases, Signal Transduction, Time Factors, Transfection, Tyrosine
J. Biol. Chem.
Date: Dec. 15, 2000
PubMed ID: 10991949
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