Transforming growth factor-β-mediated mast cell migration depends on mitogen-activated protein kinase activity
Transforming growth factor-β-mediated mast cell migration depends on mitogen-activated protein kinase activity
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DOI：
10.1016/s0898-6568(01)00176-0
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发表时间：
2001-07-01
影响因子：
4.8
通讯作者：
Nilsson, G
中科院分区：
文献类型：
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作者：
Olsson, N;Piek, E;Nilsson, G
转化生长因子-β亚型通过与具有丝氨酸/苏氨酸激酶活性的受体结合来调节多种细胞功能，这些受体通过激活Smad蛋白来传递细胞内的信号。在这项研究中，我们研究了参与转化生长因子-β1介导的人肥大细胞系HMC-1的生长抑制和迁移的信号通路。转化生长因子-β1在40fm时诱导最佳迁移，而在400fm时达到最大生长抑制。蛋白酪氨酸激酶抑制剂完全抑制转化生长因子-β1介导的迁移，而不影响抗分裂反应。在没有和存在染料木素的情况下，Smad2在转化生长因子-β1处理后都被磷酸化。有丝分裂原诱导的细胞外激酶(MEK)抑制剂。PD98059在不影响生长抑制的情况下，阻断了细胞的迁移反应。相反，p38的MAP激酶抑制剂。SB203580对HMC-1细胞的迁移和生长抑制均无显著影响，这些结果表明不同的信号通路介导了转化生长因子-β1诱导的HMC-1细胞的迁移和生长抑制，其中迁移涉及MEK活性。(C)2001 Elsevier Science Inc.保留所有权利。
Transforming growth factor-beta (TGF-beta) isoforms regulate numerous cellular functions through binding to receptors with intrinsic serine/threonine kinase activity that transduce the intracellular signals via activation of Smad proteins. In this study, we examined the signalling pathways involved in TGF-beta1-mediated growth inhibition and migration in a human mast cell line, HMC-1. TGF-beta1 evoked optimal migration at 40 fM, whereas maximal growth inhibition was obtained at 400 pM. Protein tyrosine kinase inhibitors completely inhibited TGF-beta1-mediated migration, without affecting the antimitogenic response. Smad2 was phosphorylated upon TGF-beta1 treatment, both in the absence and presence of genistein. The mitogen-induced extracellular kinase (MEK) inhibitor. PD98059, blocked the migratory response without affecting growth inhibition. In contrast, the p38 MAP kinase inhibitor. SB203580, had no significant effect on either migration or growth inhibition, These results indicate that different signalling pathways mediate TGF-beta1-induced migration and growth inhibition in HMC-1 cells, where the migration involves MEK activity. (C) 2001 Elsevier Science Inc. All rights reserved.