| First Author | Takayama G | Year | 2013 |
| Journal | Int Immunol | Volume | 25 |
| Issue | 4 | Pages | 215-20 |
| PubMed ID | 23143475 | Mgi Jnum | J:194426 |
| Mgi Id | MGI:5473755 | Doi | 10.1093/intimm/dxs105 |
| Citation | Takayama G, et al. (2013) Class I PI3K-mediated Akt and ERK signals play a critical role in Fc{varepsilon}RI-induced degranulation in mast cells. Int Immunol 25(4):215-20 |
| abstractText | Class IA and IB phosphoinositide 3-kinases (PI3Ks) have been shown to regulate mast cell functions such as proliferation, development, survival and degranulation, but the functional redundancy between these two PI3K signaling pathways in mast cells remains unclear. Here, we have generated mice deficient in both class IA regulatory subunit p85alpha and class IB catalytic subunit p110gamma, and show that p85alpha(-/-)p110gamma(-/-) mice exhibit a more severe defect in mast cell development than single-knockout mice. In addition, the in vivo passive cutaneous anaphylaxis reaction of p85alpha(-/-)p110gamma(-/-) mice was nearly completely abrogated, whereas single-knockout mice exhibit just marginal reduction. Pharmacological inactivation of Akt in wild-type bone marrow-derived mast cells (BMMCs) led to partial reduction of degranulation, while over-expression of a constitutively active Akt partially restored the impaired degranulation in p85alpha(-/-)p110gamma(-/-) BMMCs. We also found that the extracellular signal-regulated kinase (ERK) signaling pathway was activated in a PI3K-dependent manner upon FcepsilonRI stimulation and that simultaneous inhibition of Akt and ERK resulted in nearly complete blockade of FcepsilonRI-induced degranulation. Our data provide evidence that Akt and ERK pathways play redundant roles in FcepsilonRI-induced degranulation. |
