Podocyte Protein, Nephrin, Is a Substrate of Protein Tyrosine Phosphatase 1B.
Podocyte Protein, Nephrin, Is a Substrate of Protein Tyrosine Phosphatase 1B.
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DOI：
10.1155/2011/376543
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Takano T
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文献类型：
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作者：
Aoudjit L;Jiang R;Lee TH;New LA;Jones N;Takano T
肾小球足细胞对于肾脏中肾小球的屏障功能至关重要，并且它们的功能障碍导致蛋白渗漏到尿中（蛋白尿）。Nephrin是一种关键的足细胞蛋白，通过胞浆结构域的酪氨酸磷酸化调节肌动蛋白细胞骨架。在这里，我们报告了两种蛋白酪氨酸磷酸酶，PTP 1B和PTP-PEST负调控nephrin酪氨酸磷酸化。PTP 1B直接结合并使nephrin脱磷酸化，而PTP-PEST的作用是间接的。在嘌呤霉素氨基核苷肾病大鼠模型中，这两种磷酸酶在肾小球中也上调。PTP 1B的过度表达和抑制都扰乱了培养的小鼠足细胞中的肌动蛋白细胞骨架。因此，蛋白酪氨酸磷酸酶可能通过调节nephrin酪氨酸磷酸化而影响足细胞功能。
Glomerular podocytes are critical for the barrier function of the glomerulus in the kidney and their dysfunction causes protein leakage into the urine (proteinuria). Nephrin is a key podocyte protein, which regulates the actin cytoskeleton via tyrosine phosphorylation of its cytoplasmic domain. Here we report that two protein tyrosine phosphatases, PTP1B and PTP-PEST negatively regulate nephrin tyrosine phosphorylation. PTP1B directly binds to and dephosphorylates nephrin, while the action of PTP-PEST is indirect. The two phosphatases are also upregulated in the glomerulus in the rat model of puromycin aminonucleoside nephrosis. Both overexpression and inhibition of PTP1B deranged the actin cytoskeleton in cultured mouse podocytes. Thus, protein tyrosine phosphatases may affect podocyte function via regulating nephrin tyrosine phosphorylation.