Chemotaxis of mast cells is one of the crucial steps in their development and function. Non-T cell activation linker (NTAL) is a transmembrane adaptor protein that inhibits the activation of mast cells and B cells in a phosphorylation-dependent manner. Here, we studied the role of NTAL in the migration of mouse mast cells stimulated by prostaglandin E2 (PGE2). Although PGE2 does not induce the tyrosine phosphorylation of NTAL, unlike IgE immune complex antigens, we found that loss of NTAL increased the chemotaxis of mast cells toward PGE2 Stimulation of mast cells that lacked NTAL with PGE2 enhanced the phosphorylation of AKT and the production of phosphatidylinositol 3,4,5-trisphosphate. In resting NTAL-deficient mast cells, phosphorylation of an inhibitory threonine in ERM family proteins accompanied increased activation of β1-containing integrins, which are features often associated with increased invasiveness in tumors. Rescue experiments indicated that only full-length, wild-type NTAL restored the chemotaxis of NTAL-deficient cells toward PGE2 Together, these data suggest that NTAL is a key inhibitor of mast cell chemotaxis toward PGE2, which may act through the RHOA/ERM/β1-integrin and PI3K/AKT axes.

中文翻译：

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跨膜衔接蛋白NTAL限制肥大细胞对前列腺素E2的趋化性。

肥大细胞的趋化性是其发育和功能的关键步骤之一。非T细胞活化接头（NTAL）是一种跨膜衔接蛋白，以依赖于磷酸化的方式抑制肥大细胞和B细胞的活化。在这里，我们研究了NTAL在前列腺素E2（PGE2）刺激的小鼠肥大细胞迁移中的作用。尽管PGE2不会诱导NTAL的酪氨酸磷酸化，与IgE免疫复合抗原不同，我们发现NTAL的缺失增加了肥大细胞对PGE2的趋化性。用PGE2刺激缺乏NTAL的肥大细胞增强了AKT的磷酸化和磷脂酰肌醇的产生。 3,4,5-三磷酸。在静止的NTAL缺乏的肥大细胞中，ERM家族蛋白中抑制性苏氨酸的磷酸化伴随着含β1整合素激活的增加，而这些特征通常与肿瘤浸润性增加有关。救援实验表明，只有全长野生型NTAL才能恢复NTAL缺陷细胞对PGE2的趋化作用，这些数据表明NTAL是肥大细胞对PGE2趋化作用的关键抑制剂，这可能是通过RHOA / ERM / β1-整合素和PI3K / AKT轴。