Recruitment of TEC kinases to p-SLP-76

Mast cells express four out of five Tec family members (i.e. BTK, ITK, RLK and TEC) and are activated upon cross-linking of FCERI. They are recruited to the membrane via the interaction of their PH domain with PtdIns(3,4,5)P3 phosphate and their SH2 domain with Y145 of SLP-76 (Kettner et al. 2003). BTK is more important for early response such as phosphorylation of PLC-gamma2 and Ca2+ mobilization, whereas ITK regulates the late responses such as changes in gene expression and cytokine secretion. BTK deficient mice have mild defects in degranulation and severe impairments in the production of proinflammatory cytokines upon FCERI cross-linking (Hata et al. 1998). ITK deficient mice have been reported to have reduced MC degranulation and responses to allergic asthma (Forssell et al. 2005). However, Bone marrow derived mast cells (BMMC) derived from ITK deficient mice display a normal degranulation response but secrete elevated level of cytokines (TNFa and IL-13) (Iyer & August 2008). TEC kinase is also one of the crucial regulators of murine mast cell function. TEC is phosphorylated and activated upon FCERI stimulation. TEC deficient bone marrow derived mast cells did not show any in vitro or in vivo defects in histamine release. However, the generation of the leukotriene LTC4 was severely impaired in the absence of TEC (Schmidt et al. 2009).

肥大细胞表达Tec家族的四个成员（即BTK、ITK、RLK和TEC），并在FCERI的交联作用下被激活。通过其PH结构域与PtdIns(3,4,5)P3磷酸基团的相互作用及其SH2结构域与SLP-76的Y145位点的相互作用，它们被招募到细胞膜上（Kettner等，2003年）。BTK对于早期反应（如PLC-gamma2的磷酸化和Ca2+的动员）更为重要，而ITK则调节晚期反应，如基因表达和细胞因子分泌的改变。BTK缺陷型小鼠在FCERI交联后表现出轻微的脱颗粒缺陷和严重的前炎症细胞因子生成障碍（Hata等，1998年）。ITK缺陷型小鼠据报道具有减少的肥大细胞脱颗粒和对过敏性哮喘的反应（Forssell等，2005年）。然而，由ITK缺陷型小鼠骨髓衍生的肥大细胞（BMMC）表现出正常的脱颗粒反应，但分泌了升高的细胞因子（TNFa和IL-13）水平（Iyer & August，2008年）。TEC激酶也是调控小鼠肥大细胞功能的关键调节因子。TEC在FCERI刺激下被磷酸化和激活。TEC缺陷型骨髓衍生的肥大细胞在体外或体内均未显示出组胺释放方面的缺陷。然而，在缺乏TEC的情况下，白三烯LTC4的生成严重受损（Schmidt等，2009年）。