Role of Plasmodium falciparum thrombospondin-related anonymous protein in host-cell interactions.
Role of Plasmodium falciparum thrombospondin-related anonymous protein in host-cell interactions.
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DOI：
10.1186/1475-2875-7-63
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发表时间：
2008-04-22
期刊：
影响因子：
3
通讯作者：
Sharma A
中科院分区：
文献类型：
--
作者：
Akhouri RR;Sharma A;Malhotra P;Sharma A
凝血酶敏感蛋白相关无名蛋白（TRAP）是子孢子运动和肝细胞侵袭所必需的。TRAP是一种1型膜蛋白，在其胞外区具有多个粘附结构域。恶性疟原虫TRAP（PfTRAP）及其亚结构域在哺乳动物表达系统中表达，并产生11种不同的突变体，以研究PfTRAP与肝细胞的相互作用。使用免疫共沉淀方案进行HepG 2细胞提取物和PfTRAP之间的结合研究。已经鉴定了参与肝细胞结合的PfTRAP的五种不同氨基酸残基。这些PfTRAP突变体与野生型PfTRAP一样与肝素结合，从而表明PfTRAP与肝细胞的结合是非肝素介导的。还鉴定了与PfTRAP相互作用的三种Src家族蛋白--林恩、Lck和CrkL。肝细胞提取物和免疫沉淀Src家族激酶在多个位点磷酸化PfTRAP。多个TRAP序列的分析揭示了Src同源3结构域（SH 3）结合基序。PfTRAP与含SH 3结构域的蛋白质如Src家族激酶的结合及其磷酸化PfTRAP的能力表明PfTRAP在子孢子侵入和归巢肝细胞内的细胞信号传导中的新作用。这些数据为TRAP-肝细胞相互作用提供了新的线索。
Thrombospondin-related anonymous protein (TRAP) is essential for sporozoite motility and for liver cell invasion. TRAP is a type 1 membrane protein that possesses multiple adhesive domains in its extracellular region. Plasmodium falciparum TRAP (PfTRAP) and its subdomains were expressed in a mammalian expression system, and eleven different mutants generated to study interaction of PfTRAP with liver cells. Binding studies between HepG2 cell extracts and PfTRAP were performed using co-immunoprecipitation protocols. Five different amino acid residues of PfTRAP that are involved in liver cell binding have been identified. These PfTRAP mutants bound to heparin like the wild type PfTRAP thereby suggesting a non-heparin mediated binding of PfTRAP to liver cells. Three Src family proteins -Lyn, Lck and CrkL which interact with PfTRAP are also identified. Liver cell extracts and immunoprecipitated Src family kinases phosphorylated PfTRAP at multiple sites. An analysis of multiple TRAP sequences revealed Src homology 3 domain (SH3) binding motifs. Binding of PfTRAP to SH3-domain containing proteins like Src-family kinases and their ability to phosphorylate PfTRAP suggests a novel role for PfTRAP in cell signaling during sporozoite invasion and homing inside the liver cells. These data shed new light on TRAP-liver cell interactions.
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影响因子：
4.1
作者：
Akhouri, RR;Bhattacharyya, A;Sharma, A
通讯作者：
Sharma, A
影响因子：
1.5
作者：
Frevert, U;Sinnis, P;Nussenzweig, V
通讯作者：
Nussenzweig, V
影响因子：
1.5
作者：
McCormick, CJ;Tuckwell, DS;Hollingdale, MR
通讯作者：
Hollingdale, MR
影响因子：
3.1
作者：
Gantt, S;Persson, C;Nussenzweig, V
通讯作者：
Nussenzweig, V
影响因子：
64.8
作者：
ROBSON, KJH;HALL, JRS;WEATHERALL, DJ
通讯作者：
WEATHERALL, DJ