Wu Z, Cavallaro U, Marchisio P C, Soria M R, Maier J A
Department of Biological and Technicological Research, San Rafaele Scientific Institute, Milan, Italy.
Am J Pathol. 1998 Jun;152(6):1599-605.
HIV-1 Tat plays a role in the pathogenesis of Kaposi's sarcoma. We therefore investigated the effect of Tat on the growth of murine Kaposi's sarcoma-like spindle (TTB) cells derived from dermal lesions. We observed that Tat and a peptide corresponding to the carboxyl-terminal region (Tat65-80) containing an RGD sequence inhibit TTB cell proliferation only when cells are cultured on fibronectin. This inhibitory effect correlates with redistribution of the alpha(v) integrin subunit on the surface of TTB cells and with down-regulation of tyrosine phosphorylation of specific substrates due to an increased tyrosine phosphatase activity. Indeed, phenylarsine oxide, a potent inhibitor of phosphotyrosine phosphatases, prevented the effects of Tat on TTB cells. We therefore argue that the action of Tat on TTB cells is mediated by the RGD motif through an integrin-based cell signaling pathway involving the activity of phosphotyrosine phosphatase(s), which would lead to a decrease in the levels of phosphotyrosine-containing proteins, among which is erk-2/p42MAPK.
HIV-1反式激活因子（Tat）在卡波西肉瘤的发病机制中起作用。因此，我们研究了Tat对源自皮肤病变的小鼠卡波西肉瘤样纺锤体（TTB）细胞生长的影响。我们观察到，只有当细胞在纤连蛋白上培养时，Tat和一个对应于含RGD序列的羧基末端区域（Tat65 - 80）的肽才会抑制TTB细胞增殖。这种抑制作用与TTB细胞表面α(v)整合素亚基的重新分布以及由于酪氨酸磷酸酶活性增加导致的特定底物酪氨酸磷酸化的下调相关。事实上，苯砷氧化物是一种有效的磷酸酪氨酸磷酸酶抑制剂，它可阻止Tat对TTB细胞的作用。因此，我们认为Tat对TTB细胞的作用是通过RGD基序，经由基于整合素的细胞信号通路介导的，该信号通路涉及磷酸酪氨酸磷酸酶的活性，这会导致含磷酸酪氨酸的蛋白质水平降低，其中包括erk - 2/p42MAPK。
