| First Author | Nakata K | Year | 2008 |
| Journal | J Immunol | Volume | 181 |
| Issue | 8 | Pages | 5414-24 |
| PubMed ID | 18832698 | Mgi Jnum | J:140765 |
| Mgi Id | MGI:3814516 | Doi | 10.4049/jimmunol.181.8.5414 |
| Citation | Nakata K, et al. (2008) Positive and negative regulation of high affinity IgE receptor signaling by Src homology region 2 domain-containing phosphatase 1. J Immunol 181(8):5414-24 |
| abstractText | Src homology region 2 domain-containing phosphatase 1 (SHP-1), a cytoplasmic protein tyrosine phosphatase, plays an important role for the regulation of signaling from various hematopoietic cell receptors. Although SHP-1 is shown to be a negative signal modulator in mast cells, its precise molecular mechanisms are not well defined. To elucidate how SHP-1 regulates mast cell signaling, we established bone marrow-derived mast cells from SHP-1-deficient motheaten and wild-type mice and analyzed downstream signals induced by cross-linking of high affinity IgE receptor, Fc epsilonRI. Upon Fc epsilonRI ligation, motheaten-derived bone marrow-derived mast cells showed enhanced tyrosine phosphorylation of Src homology region 2 domain-containing leukocyte protein of 76 kDa (SLP-76) and linker for activation of T cells, activation of mitogen-activated protein kinases and gene transcription and production of cytokine. Because the activity of Syk, responsible for the phosphorylation of SLP-76 and linker for activation of T cells, is comparable irrespective of SHP-1, both molecules might be substrates of SHP-1 in mast cells. Interestingly, the absence of SHP-1 expression disrupted the association between SLP-76 and phospholipase Cgamma, which resulted in the decreased phospholipase Cgamma phosphorylation, calcium mobilization, and degranulation. Collectively, these results suggest that SHP-1 regulates Fc epsilonRI-induced downstream signaling events both negatively and positively by functioning as a protein tyrosine phosphatase and as an adaptor protein contributing to the formation of signaling complex, respectively. |
