A new family of receptor tyrosine kinases with a venus flytrap binding domain in insects and other invertebrates activated by aminoacids.

A new family of receptor tyrosine kinases with a venus flytrap binding domain in insects and other invertebrates activated by aminoacids.
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DOI:
10.1371/journal.pone.0005651
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发表时间:
2009-05-21
期刊:
影响因子:
3.7
通讯作者:
Dissous C
Dissous C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ahier A;Rondard P;Gouignard N;Khayath N;Huang S;Trolet J;Donoghue DJ;Gauthier M;Pin JP;Dissous C

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酪氨酸激酶受体(RTK)包括调节不同生物体的细胞生物学中的各种细胞过程的膜受体的大家族。我们以前描述了一种非典型RTK在扁形动物寄生虫曼氏血吸虫,由一个细胞外捕蝇草模块(VFT)连接通过一个单一的跨膜结构域的细胞内酪氨酸激酶结构域类似的胰岛素受体。在这里,我们表明,这种受体是在无脊椎动物中发现的一个新的RTK家族的成员,特别是在昆虫中。在许多昆虫中发现了16个新成员,命名为维纳斯激酶受体(Venus Kinase Receptor,VKR)。对VFT和TK结构域进行的结构和系统发育研究表明,VKR序列形成单系群,VFT群接近GABAB受体,TK群接近胰岛素受体。我们表明,重组VKR是能够自磷酸化的酪氨酸残基,并报告说,它可以被激活的L-精氨酸。这与在许多氨基酸结合VFT中发现的α氨基酸结合残基的高度保守性一致。在幼虫形式和雌性性腺中存在高水平的vkr转录物表明VKR在生殖和/或发育中的推定功能。对寄生虫和昆虫媒介特异性RTKs的鉴定为人类寄生虫和传染病的控制提出了新的观点。
Tyrosine kinase receptors (RTKs) comprise a large family of membrane receptors that regulate various cellular processes in cell biology of diverse organisms. We previously described an atypical RTK in the platyhelminth parasite Schistosoma mansoni, composed of an extracellular Venus flytrap module (VFT) linked through a single transmembrane domain to an intracellular tyrosine kinase domain similar to that of the insulin receptor. Here we show that this receptor is a member of a new family of RTKs found in invertebrates, and particularly in insects. Sixteen new members of this family, named Venus Kinase Receptor (VKR), were identified in many insects. Structural and phylogenetic studies performed on VFT and TK domains showed that VKR sequences formed monophyletic groups, the VFT group being close to that of GABAB receptors and the TK one being close to that of insulin receptors. We show that a recombinant VKR is able to autophosphorylate on tyrosine residues, and report that it can be activated by L-arginine. This is in agreement with the high degree of conservation of the alpha amino acid binding residues found in many amino acid binding VFTs. The presence of high levels of vkr transcripts in larval forms and in female gonads indicates a putative function of VKR in reproduction and/or development. The identification of RTKs specific for parasites and insect vectors raises new perspectives for the control of human parasitic and infectious diseases.
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期刊: BIOINFORMATICS
影响因子: 5.8
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发表时间: 2004-07-20
影响因子: 11.1
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