PTEN controls immunoreceptor (immunoreceptor tyrosine-based activation motif) signaling and the activation of Rac
PTEN controls immunoreceptor (immunoreceptor tyrosine-based activation motif) signaling and the activation of Rac
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DOI：
10.1182/blood.v99.2.694
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发表时间：
2002-01-15
期刊：
影响因子：
20.3
通讯作者：
Durden, DL
中科院分区：
文献类型：
--
作者：
Kim, JS;Peng, XD;Durden, DL
Fc γ受体介导的吞噬作用是研究免疫受体（基于免疫受体酪氨酸的活化基序[ITAM]）信号传导的模型，涉及蛋白酪氨酸激酶、蛋白酪氨酸磷酸酶和下游效应物（包括磷脂酰肌醇-3（PI-3）激酶）的活化。相对较少的是已知的脂质磷酸酶在控制[ITAM]信号和炎症的作用。使用异源C 0 S7细胞系统来检查PI-3激酶和双特异性磷酸酶、10号染色体上缺失的磷酸酶和张力蛋白同源物（PTEN）在导致Fc γ受体IIA介导的吞噬作用和Rac活化的信号转导途径中所起的作用。野生型PTEN的表达完全废除了免疫球蛋白G致敏的绵羊红细胞的吞噬作用，相比之下，催化失活的突变体的PTEN，没有效果。这是第一个直接证据表明，PTEN，肌醇3'磷酸酶，调节Fc γ受体介导的吞噬作用，ITAM为基础的信号转导事件。这些数据表明，PTEN可能通过控制ITAM刺激后鸟苷二磷酸-Rac向鸟苷三磷酸-Rac的下游转化来控制吞噬作用。（血。2002;99：694-697）（C）2002年由美国血液学会。
Fcgamma receptor-mediated phagocytosis is a model for the study of immunoreceptor (immunoreceptor tyrosine-based activation motif [ITAM]) signaling and involves the activation of protein tyrosine kinases, protein tyrosine phosphatases, and downstream effectors including phosphatidylinositol-3 (PI-3) kinase. Relatively little is known of the role of lipid phosphatases in the control of [ITAM] signaling and inflammation. A heterologous COS7 cell system was used to examine the roles played by PI-3 kinase and the dual-specificity phosphatase, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), in the signal transduction pathway leading to Fcgamma receptor IIA-mediated phagocytosis and the activation of Rac. The expression of wildtype PTEN completely abrogated the phagocytosis of immunoglobulin-G-sensitized sheep red blood cells, as compared with the catalytically inactive mutant of PTEN, which had no effect. This is the first direct evidence that PTEN, an inositol 3' phosphatase, regulates Fcgamma receptor-mediated phagocytosis, an ITAM-based signaling event. The data suggest that PTEN exerts control over phagocytosis potentially by controlling the downstream conversion of guanosine diphosphate-Rac to guanosine triphosphate-Rac following ITAM stimulation. (Blood. 2002;99: 694-697) (C) 2002 by The American Society of Hematology.