The role of protein tyrosine phosphorylation in integrin-mediated gene induction in monocytes.
The role of protein tyrosine phosphorylation in integrin-mediated gene induction in monocytes.
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DOI：
10.1083/jcb.126.6.1585
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发表时间：
1994-09
期刊：
影响因子：
--
通讯作者：
Juliano RL
中科院分区：
文献类型：
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作者：
Lin TH;Yurochko A;Kornberg L;Morris J;Walker JJ;Haskill S;Juliano RL
整合素介导的细胞粘附，或使用抗体的整合素交联，通常会导致某些细胞内蛋白的酪氨酸磷酸化增强，这表明整合素可能在信号转导过程中发挥作用。在成纤维细胞、血小板和癌细胞中，一种名为pp125FAK的新型酪氨酸激酶与整合素介导的酪氨酸磷酸化有关。在某些细胞类型中，整合素连接或细胞粘附也被证明会导致某些基因的表达增加。虽然整合素介导的酪氨酸磷酸化与整合素介导的基因诱导相关的假设似乎是合理的，但到目前为止，还没有直接的证据支持这一假设。在本报告中，我们探讨了整合素介导的酪氨酸磷酸化与人类单核细胞基因诱导之间的关系。我们证明，单核细胞粘附于组织培养皿或细胞外基质蛋白之后，酪氨酸磷酸化迅速而深刻地增加，主要磷酸化成分是76 kD （pp76）的蛋白。整合素- 1亚基抗体或此类抗体的F（ab’）2片段孵育单核细胞也可触发pp76和其他单核细胞蛋白的酪氨酸磷酸化，但F（ab）片段不会触发。β 1整合素与抗体或F(ab')2片段的连接也诱导了即时早期（IE）基因如IL-1 β的表达。当黏附单核细胞用酪氨酸激酶抑制剂染料木素或赫比霉素处理时，pp76的磷酸化和IL-1 β信号的诱导都以剂量依赖性的方式被阻断。同样，用染料木素或herbyycin治疗可以阻断pp76的酪氨酸磷酸化和β 1整合素与抗体连接介导的IL-1 β信息诱导。这些观察结果表明，蛋白酪氨酸磷酸化是整合素介导的单核细胞IE基因诱导的一个重要方面。细胞质酪氨酸激酶pp125FAK虽然在其他细胞类型的整合素信号传导中很重要，但似乎在单核细胞中不起作用，因为在这些细胞中无法检测到该蛋白。
Integrin-mediated cell adhesion, or cross-linking of integrins using antibodies, often results in the enhanced tyrosine phosphorylation of certain intracellular proteins, suggesting that integrins may play a role in signal transduction processes. In fibroblasts, platelets, and carcinoma cells, a novel tyrosine kinase termed pp125FAK has been implicated in integrin-mediated tyrosine phosphorylation. In some cell types, integrin ligation or cell adhesion has also been shown to result in the increased expression of certain genes. Although it seems reasonable to hypothesize that integrin-mediated tyrosine phosphorylation and integrin-mediated gene induction are related, until now, there has been no direct evidence supporting this hypothesis. In the current report, we explore the relationship between integrin- mediated tyrosine phosphorylation and gene induction in human monocytes. We demonstrate that monocyte adherence to tissue culture dishes or to extracellular matrix proteins is followed by a rapid and profound increase in tyrosine phosphorylation, with the predominant phosphorylated component being a protein of 76 kD (pp76). Tyrosine phosphorylation of pp76 and other monocyte proteins can also be triggered by incubation of monocytes with antibodies to the integrin beta 1 subunit, or by F(ab')2 fragments of such antibodies, but not by F(ab) fragments. The ligation of beta 1 integrins with antibodies or F(ab')2 fragments also induces the expression of immediate-early (IE) genes such as IL-1 beta. When adhering monocytes are treated with the tyrosine kinase inhibitors genistein or herbimycin, both phosphorylation of pp76 and induction of IL-1 beta message are blocked in a dose-dependent fashion. Similarly, treatment with genistein or herbimycin can block tyrosine phosphorylation of pp76 and IL-1 beta message induction mediated by ligation of beta 1 integrin with antibodies. These observations suggest that protein tyrosine phosphorylation is an important aspect of integrin-mediated IE gene induction in monocytes. The cytoplasmic tyrosine kinase pp125FAK, although important in integrin signaling in other cell types, seems not to play a role in monocytes because this protein could not be detected in these cells.