LAX is a transmembrane adaptor protein that is expressed in both T and B cells. Upon stimulation via the antigen receptors, it is tyrosine-phosphorylated and binds Grb2 and the p85 subunit of phosphatidylinositol 3-kinase. Disruption of the Lax gene causes hyperresponsiveness in T and B lymphocytes. Here, we showed that LAX was also expressed in mast cells. Upon engagement of the Fc epsilonRI, LAX was also phosphorylated and interacted with Grb2 and p85. LAX-deficient mast cells were hyperresponsive to stimulation via the Fc epsilonRI, as evidenced by enhanced degranulation, p38 MAPK, Akt, and phosphatidylinositol 3-kinase activation. This hyperresponsiveness was likely a consequence of reduced LAB expression after sensitization of mast cells with anti-dinitrophenyl IgE. In addition, Fc epsilonRI-mediated cytokine production and cell survival were also enhanced. These data suggested that LAX negatively regulates mast cell function.
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机译：LAX 是一种跨膜接头蛋白，在 T 细胞和 B 细胞中均表达。在通过抗原受体刺激后，它被酪氨酸磷酸化并结合 Grb2 和磷脂酰肌醇 3-激酶的 p85 亚基。Lax 基因的破坏会导致 T 淋巴细胞和 B 淋巴细胞的高反应性。在这里，我们发现LAX也在肥大细胞中表达。在 Fc epsilonRI 结合后，LAX 也被磷酸化并与 Grb2 和 p85 相互作用。LAX 缺陷肥大细胞对 Fc epsilonRI 的刺激反应过高，如增强的脱颗粒、p38 MAPK、Akt 和磷脂酰肌醇 3-激酶激活所证明的那样。这种高反应性可能是肥大细胞用抗二硝基苯基 IgE 致敏后 LAB 表达降低的结果。此外，FcεRN介导的细胞因子产生和细胞存活也得到增强。这些数据表明，LAX负向调节肥大细胞功能。
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