Positive Effect of Overexpressed Protein-tyrosine Phosphatase PTP1C on Mitogen-activated Signaling in 293 Cells (*)
Positive Effect of Overexpressed Protein-tyrosine Phosphatase PTP1C on Mitogen-activated Signaling in 293 Cells (*)
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DOI：
10.1074/jbc.271.17.10385
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发表时间：
1996-04
期刊：
影响因子：
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通讯作者：
Long Su;Z. Zhao;P. Bouchard;D. Banville;E. Fischer;E. Krebs;S. Shen
中科院分区：
文献类型：
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作者：
Long Su;Z. Zhao;P. Bouchard;D. Banville;E. Fischer;E. Krebs;S. Shen
PTP 1C是一种含有SH 2结构域的蛋白酪氨酸磷酸酶，主要在造血细胞中表达，它负调节细胞信号传导。然而，这种酶也在许多非造血细胞中表达。我们在这里证明，在非造血293细胞中，过度表达的催化失活突变体的PTP 1C强烈抑制表皮生长因子或血清对细胞增殖，早期基因转录和DNA合成的刺激作用。同样，有丝分裂原活化蛋白激酶和有丝分裂原活化蛋白激酶激酶活性的磷酸化显着抑制突变体PTP 1C的过表达。突变体PTP 1C的抑制作用被克服与野生型PTP 1C的共转染，但不是与结构相关的PTP 2C。此外，突变体磷酸酶的表达导致在一个95-kDa的蛋白，是共免疫沉淀的突变体，但不是与野生型蛋白的酪氨酸过度磷酸化。这些结果表明，与造血细胞不同，293细胞中的PTP 1C在表皮生长因子或血清激活的有丝分裂中起着积极的作用。因此，PTP 1C参与多种信号传导途径，其中酶取决于其靶分子，可以作为正或负介体发挥作用。
PTP1C, an SH2 domain-containing protein-tyrosine phosphatase, is predominantly expressed in hematopoietic cells, in which it negatively regulates cellular signaling. However, this enzyme is also expressed in many non-hematopoietic cells. We demonstrate here that in non-hematopoietic 293 cells, overexpression of a catalytically inactive mutant of PTP1C strongly suppressed the stimulatory effects of the epidermal growth factor or serum on cell proliferation, early gene transcription, and DNA synthesis. Similarly, the phosphorylation of the mitogen-activated protein kinase and mitogen-activated protein kinase kinase activity was markedly inhibited by overexpression of mutant PTP1C. The inhibitory effect of mutant PTP1C was overcome by cotransfection with wild-type PTP1C, but not with the structurally related PTP2C. Furthermore, expression of the mutant phosphatase resulted in hyperphosphorylation on tyrosine of a 95-kDa protein that was co-immunoprecipitated with the mutant, but not with the wild-type protein. These results suggest that, unlike in hematopoietic cells, PTP1C in 293 cells plays a positive role in epidermal growth factor- or serum-activated mitogenesis. Thus, PTP1C participates in multiple signaling pathways, where the enzyme, depending on its target molecules, may function as either a positive or negative mediator.