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首页> 外文期刊>Molecular and Cellular Biology >Site-Selective Regulation of Platelet-Derived Growth Factor β Receptor Tyrosine Phosphorylation by T-Cell Protein Tyrosine Phosphatase
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Site-Selective Regulation of Platelet-Derived Growth Factor β Receptor Tyrosine Phosphorylation by T-Cell Protein Tyrosine Phosphatase

机译：T细胞蛋白酪氨酸磷酸酶对血小板衍生生长因子β受体酪氨酸磷酸化的位点选择性调节

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The platelet-derived growth factor (PDGF) β receptor mediates mitogenic and chemotactic signals. Like other tyrosine kinase receptors, the PDGF β receptor is negatively regulated by protein tyrosine phosphatases (PTPs). To explore whether T-cell PTP (TC-PTP) negatively regulates the PDGF β receptor, we compared PDGF β receptor tyrosine phosphorylation in wild-type and TC-PTP knockout (ko) mouse embryos. PDGF β receptors were hyperphosphorylated in TC-PTP ko embryos. Fivefold-higher ligand-induced receptor phosphorylation was observed in TC-PTP ko mouse embryo fibroblasts (MEFs) as well. Reexpression of TC-PTP partly abolished this difference. As determined with site-specific phosphotyrosine antibodies, the extent of hyperphosphorylation varied among different autophosphorylation sites. The phospholipase Cγ1 binding site Y1021, previously implicated in chemotaxis, displayed the largest increase in phosphorylation. The increase in Y1021 phosphorylation was accompanied by increased phospholipase Cγ1 activity and migratory hyperresponsiveness to PDGF. PDGF β receptor tyrosine phosphorylation in PTP-1B ko MEFs but not in PTPε ko MEFs was also higher than that in control cells. This increase occurred with a site distribution different from that seen after TC-PTP depletion. PDGF-induced migration was not increased in PTP-1B ko cells. In summary, our findings identify TC-PTP as a previously unrecognized negative regulator of PDGF β receptor signaling and support the general notion that PTPs display site selectivity in their action on tyrosine kinase receptors.
机译：血小板衍生的生长因子（PDGF）β受体介导有丝分裂和趋化信号。像其他酪氨酸激酶受体一样，PDGFβ受体受到蛋白质酪氨酸磷酸酶（PTP）的负调控。为了探讨T细胞PTP（TC-PTP）是否负调节PDGFβ受体，我们比较了野生型和TC-PTP敲除（ko）小鼠胚胎中PDGFβ受体酪氨酸的磷酸化。 PDGFβ受体在TC-PTP ko胚胎中被过度磷酸化。在TC-PTP ko小鼠胚胎成纤维细胞（MEF）中也观察到配体诱导的受体磷酸化高五倍。 TC-PTP的重新表达部分消除了这种差异。如用位点特异性磷酸酪氨酸抗体确定的，高磷酸化程度在不同的自磷酸化位点之间变化。以前与趋化性有关的磷脂酶Cγ1结合位点Y1021表现出最大的磷酸化增加。 Y1021磷酸化的增加伴随着磷脂酶Cγ1活性的增加和对PDGF的迁徙性高反应性。 PTP-1B ko MEFs中的PDGFβ受体酪氨酸磷酸化高于PTPεBko MEFs中的PDGFβ受体酪氨酸磷酸化也高于对照细胞。这种增加发生的位置与TC-PTP耗尽后的分布不同。 PDGF诱导的迁移在PTP-1B ko细胞中没有增加。总而言之，我们的发现将TC-PTP鉴定为PDGFβ受体信号传导的先前未被认识的负调节剂，并支持PTP在其对酪氨酸激酶受体的作用中显示出位点选择性的一般观点。

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