Human immunodeficiency virus Tat modulates the Flk-1/KDR receptor, mitogen-activated protein kinases, and components of focal adhesion in Kaposi's sarcoma cells
Human immunodeficiency virus Tat modulates the Flk-1/KDR receptor, mitogen-activated protein kinases, and components of focal adhesion in Kaposi's sarcoma cells
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DOI：
10.1128/jvi.72.7.6131-6137.1998
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发表时间：
1998-07-01
影响因子：
5.4
通讯作者：
Groopman, JE
中科院分区：
文献类型：
--
作者：
Ganju, RK;Munshi, N;Groopman, JE
卡波西肉瘤（KS）梭形细胞的生长和扩散已被报道受到多种细胞因子以及人类免疫缺陷病毒（HIV）基因产物达特的调节。最近，HIV-1达特已显示出像细胞因子一样起作用，并结合KS细胞表达的血管内皮生长因子A（VEGF-A）的Flk-1/KDR受体。我们的特征信号转导途径刺激HIV-1达特后，其结合到KS细胞表面受体。我们观察到，刺激KS 38梭形细胞导致酪氨酸磷酸化和激活的Flk-1/KDR受体。我们还报道了HIV-1达特治疗增强了粘连灶中蛋白质的磷酸化和结合，如相关的粘连灶酪氨酸激酶RAFTK、桩蛋白和p130（cas）。进一步的表征揭示了丝裂原活化蛋白激酶、c-Jun氨基末端激酶（JNK）和Src激酶的活化。HIV-1达特含有可与生长因子酪氨酸激酶受体相互作用的碱性结构域和可结合并活化纤连蛋白和玻连蛋白的表面整联蛋白受体的经典RGD序列，我们观察到用碱性和含RGD序列的达特肽刺激KS细胞导致RAFTK磷酸化增强和MAP激酶活化，这些研究表明，达特刺激激活了许多与细胞生长和迁移相关的信号转导途径。
Kaposi's sarcoma (KS) spindle cell growth and spread have been reported to be modulated by various cytokines as well as the human immunodeficiency virus (HIV) gene product Tat. Recently, HIV-1 Tat has been shown to act like a cytokine and bind to the Flk-1/KDR receptor for the vascular endothelial growth factor A (VEGF-A), which is expressed by KS cells. We have characterized signal transduction pathways stimulated by HIV-1 Tat upon its binding to surface receptors on KS cells. We observed that stimulation in KS 38 spindle cells resulted in tyrosine phosphorylation and activation of the Flk-1/KDR receptor. We also report that HIV-1 Tat treatment enhanced the phosphorylation and association of proteins found in focal adhesions, such as the related adhesion focal tyrosine kinase RAFTK, paxillin, and p130(cas). Further characterization revealed the activation of mitogen-activated protein kinase, c-Jun amino-terminal kinase (JNK), and Src kinase, HIV-1 Tat contains a basic domain which can interact with growth factor tyrosine kinase receptors and a classical RGD sequence which may bind to and activate the surface integrin receptors for fibronectin and vitronectin, We observed that stimulation of KS cells with basic as well as RGD sequence-containing Tat peptides resulted in enhanced phosphorylation of RAFTK and activation of MAP kinase, These studies reveal that Tat stimulation activates a number of signal transduction pathways that are associated with cell growth and migration.