| First Author | Leung WH | Year | 2007 |
| Journal | J Immunol | Volume | 179 |
| Issue | 1 | Pages | 95-102 |
| PubMed ID | 17579026 | Mgi Jnum | J:149424 |
| Mgi Id | MGI:3848435 | Doi | 10.4049/jimmunol.179.1.95 |
| Citation | Leung WH, et al. (2007) The inositol 5'-phosphatase SHIP-2 negatively regulates IgE-induced mast cell degranulation and cytokine production. J Immunol 179(1):95-102 |
| abstractText | Aggregation of the high-affinity IgE receptor (FcepsilonRI) on mast cells initiates signaling pathways leading to degranulation and cytokine release. It has been reported that SHIP-1 negatively regulates FcepsilonRI-triggered pathways but it is unknown whether its homologous protein SHIP-2 has the same function. We have used a lentiviral-based RNA interference technique to obtain SHIP-2 knockdown bone marrow-derived mast cells (BMMCs) and have found that elimination of SHIP-2 results in both increased mast cell degranulation and cytokine (IL-4 and IL-13) gene expression upon FcepsilonRI stimulation. Elimination of SHIP-2 from BMMCs has no effect on FcepsilonRI-triggered calcium flux, tyrosine phosphorylation of MAPKs or in actin depolymerization following activation. Rather, we observe that absence of SHIP-2 results in increased activation of the small GTPase Rac-1 and in enhanced microtubule polymerization upon FcepsilonRI engagement. Coimmunoprecipitation experiments in rat basophilic leukemia (RBL 2H3) cells show that SHIP-2 interacts with the FcepsilonRI beta-chain, Gab2 and Lyn and that unlike SHIP-1, it does not associate with SHC in mast cells. Our results report a negative regulatory role of SHIP-2 on mast cell activation that is calcium independent and distinct from the regulation by SHIP-1. |
