T cell activation is reduced by the catalytically inactive form of protein tyrosine phosphatase SHP-2
T cell activation is reduced by the catalytically inactive form of protein tyrosine phosphatase SHP-2
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蛋白酪氨酸磷酸酶 SHP-2 的催化失活形式会减少 T 细胞的活化
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发表时间：
2015
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通讯作者：
董宝侠
中科院分区：
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作者：
董宝侠
含Src同源2结构域的酪氨酸磷酸酶-2（SHP-2）是一种广泛表达的胞质酪氨酸磷酸酶，涉及许多不同的信号传导途径，包括细胞因子受体和T和B细胞受体;然而，SHP-2在T细胞信号传导中的精确功能作用尚不完全清楚。在这项研究中，我们过表达了一个典型的半胱氨酸459丝氨酸突变（dnSHP-2）的SHP-2的催化失活形式，以阐明SHP-2对T细胞的体内作用。我们发现过表达dnSHP-2的小鼠显示T细胞活化减少，推测是由于Grb 2结合蛋白（Gab 2）的酪氨酸磷酸化增加和丝裂原活化蛋白激酶（MAPK）活性抑制。SHP-2似乎是T细胞中MAPK途径的正调节剂，可能通过多聚体复合物与Ras/MAPK途径的偶联。然而，SHP-2似乎不影响T细胞抗原受体（TCR）诱导的钙动员，应激活化蛋白激酶/c-jun N-末端激酶（SAPK/JNKs）激活，或整体酪氨酸磷酸化。
Src-homology 2 domain-containing tyrosine phosphatase-2 (SHP-2) is a ubiquitously expressed cytosolic tyrosine phosphatase implicated in many different signaling pathways involving cytokine receptors and T and B cell receptors; however, the precise functional role of SHP-2 in T cell signaling is not entirely clear. In this study, we overexpressed a catalytically inactive form of SHP-2 with a classic cysteine 459-to-serine mutation (dnSHP-2) to elucidate the in vivo effects of SHP-2 on T cells. We found that mice overexpressing dnSHP-2 showed reduced T cell activation, presumably due to increased tyrosine phosphorylation of Grb2-binding protein (Gab2) and inhibition of mitogen-activated protein kinase (MAPK) activity. SHP-2 appears to be a positive regulator of the MAPK pathway in T cells, likely through coupling of the multimeric complex to the Ras/MAPK pathway. However, SHP-2 does not appear to affect T cell antigen receptor (TCR)-evoked calcium mobilization, stress-activated protein kinase/c-jun N-terminal kinases (SAPK/JNKs) activation, or overall tyrosine phosphorylation.