| First Author | Chihara K | Year | 2011 |
| Journal | Genes Cells | Volume | 16 |
| Issue | 12 | Pages | 1133-45 |
| PubMed ID | 22077594 | Mgi Jnum | J:191387 |
| Mgi Id | MGI:5461624 | Doi | 10.1111/j.1365-2443.2011.01557.x |
| Citation | Chihara K, et al. (2011) Association of 3BP2 with SHP-1 regulates SHP-1-mediated production of TNF-alpha in RBL-2H3 cells. Genes Cells 16(12):1133-45 |
| abstractText | Adaptor protein 3BP2, a c-Abl Src homology 3 (SH3) domain-binding protein, is tyrosine phosphorylated and positively regulates mast cell signal transduction after the aggregation of the high affinity IgE receptor (FcepsilonRI). Overexpression of the Src homology 2 (SH2) domain of 3BP2 results in the dramatic suppression of antigen-induced degranulation in rat basophilic leukemia RBL-2H3 cells. Previously, a linker for activation of T cells (LAT) was identified as one of the 3BP2 SH2 domain-binding protein. In this report, to further understand the functions of 3BP2 in FcepsilonRI-mediated activation of mast cell, we explored the protein that associates with the SH2 domain of 3BP2 and found that SH2 domain-containing phosphatase-1 (SHP-1) inducibly interacts with the SH2 domain of 3BP2 after the aggregation of FcepsilonRI. The phosphorylation of Tyr(564) in the carboxy (C)-terminal tail region of SHP-1 is required for the direct interaction of SHP-1 to the SH2 domain of 3BP2. The expression of the mutant form of SHP-1 which was unable to interact with 3BP2 resulted in the significant reduction in SHP-1-mediated tumor necrosis factor-alpha (TNF-alpha) production without any effects on the degranulation in antigen-stimulated RBL-2H3 cells. These findings suggest that 3BP2 directly interacts with Tyr(564) -phosphorylated form of SHP-1 and positively regulates the function of SHP-1 in FcepsilonRI-mediated signaling in mast cells. |
