佛波醇12-肉豆蔻酸酯13-乙酸抑制人系膜细胞中的蛋白酪氨酸磷酸酶1B活性。酪氨酸磷酸化增强的一种可能机制。

Phorbol 12-myristate 13-acetic acid inhibits PTP1B activity in human mesangial cells. A possible mechanism of enhanced tyrosine phosphorylation.

作者信息

Kiyomoto H, Fouqueray B, Abboud H E, Choudhury G G

机构信息

Department of Medicine, University of Texas Health Science Center, San Antonio 78284.

出版信息

FEBS Lett. 1994 Oct 17;353(2):217-20. doi: 10.1016/0014-5793(94)01039-0.

DOI:10.1016/0014-5793(94)01039-0

PMID:7523196

Abstract

Activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetic acid (PMA) stimulates DNA synthesis in human glomerular mesangial cells. Incubation of these cells with PMA stimulates the tyrosine phosphorylation of a set of proteins ranging from 110 to 39 kDa with different time kinetics. PMA inhibits total protein tyrosine phosphatase (PTPase) activity in these cells. Immunoprecipitation of PTP1B, an intracytoplasmic tyrosine phosphatase, with subsequent assay of the immunobeads for PTPase shows a significant inhibition of its activity in PMA-treated cells. Immunoblot analysis of mesangial cell lysates using the same antibody revealed that PMA does not affect the level of this 50 kDa PTP1B protein. These data indicate that inhibition of total PTPase, and specifically PTP1B, activity may provide a mechanism for stimulation of tyrosine phosphorylation by PMA in these cells and thereby contribute to its mitogenic effect.

摘要

佛波醇12 -肉豆蔻酸酯13 -乙酸酯（PMA）激活蛋白激酶C（PKC）可刺激人肾小球系膜细胞中的DNA合成。用PMA孵育这些细胞会刺激一组分子量在110至39 kDa之间的蛋白质发生酪氨酸磷酸化，且具有不同的时间动力学。PMA抑制这些细胞中的总蛋白酪氨酸磷酸酶（PTPase）活性。用抗细胞质酪氨酸磷酸酶PTP1B进行免疫沉淀，随后对免疫珠进行PTPase活性检测，结果显示在PMA处理的细胞中其活性受到显著抑制。使用相同抗体对系膜细胞裂解物进行免疫印迹分析表明，PMA不影响这种50 kDa的PTP1B蛋白的水平。这些数据表明，总PTPase，特别是PTP1B活性的抑制可能为PMA刺激这些细胞中的酪氨酸磷酸化提供一种机制，从而有助于其促有丝分裂作用。