| First Author | Hou S | Year | 2010 |
| Journal | Mol Immunol | Volume | 48 |
| Issue | 1-3 | Pages | 89-97 |
| PubMed ID | 20956018 | Mgi Jnum | J:167084 |
| Mgi Id | MGI:4867137 | Doi | 10.1016/j.molimm.2010.09.007 |
| Citation | Hou S, et al. (2010) The PH domain adaptor protein Bam32/DAPP1 functions in mast cells to restrain FcvarepsilonRI-induced calcium flux and granule release. Mol Immunol 48(1-3):89-97 |
| abstractText | Mast cell activation triggered by IgE binding to its high affinity receptor FcvarepsilonRI is highly dependent on signaling via phosphoinositde 3-kinases (PI3K). The phosphoinositide phosphatase SHIP controls mast cell activation by regulating accumulation of D3 phosphoinositide second messengers generated by PI3K. The PH domain adaptor protein Bam32/DAPP1 binds specifically to the D3 phosphoinositides PI(3,4,5)P3 and PI(3,4)P2 (the substrate and product of SHIP respectively). In B cells, Bam32 is phosphorylated by Src family kinases including Lyn, and is required for antigen receptor-induced activation; however the function of Bam32 in mast cells is unknown. Here we report that Bam32 is expressed in mast cells, is recruited to the plasma membrane upon stimulation and functions in FcvarepsilonRI signaling. Examination of bone marrow-derived mast cells (BMMC) isolated from Bam32-deficient mice revealed enhanced FcvarepsilonRI-induced degranulation and IL-6 production, indicating that Bam32 may function to restrain signaling via FcvarepsilonRI. These enhanced degranulation responses were PI3K-dependent, as indicated by blockade with PI3K inhibitors wortmannin or IC87114. While Bam32-deficient BMMC showed reduced FcvarepsilonRI-induced activation of mitogen-activated protein kinases ERK and JNK, FcvarepsilonRI-induced calcium flux and phosphorylation of PLCgamma1 and Akt were increased. Bam32-deficient BMMC showed significantly reduced phosphorylation of Lyn and SHIP, indicating reduced activity of inhibitory signaling pathways. Together our results identify Bam32 as a novel regulator of mast cell activation, potentially functioning in membrane-proximal integration of positive and negative signaling pathways. |
