Morel Marion, Vanderstraete Mathieu, Cailliau Katia, Hahnel Steffen, Grevelding Christoph G, Dissous Colette
Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 -UMR 8204-CIIL-Center for Infection and Immunity of Lille, Lille, France.
Univ. Lille, CNRS, UMR 8576-UGSF-Unité de Glycobiologie Structurale et Fonctionnelle, Lille, France.
PLoS One. 2016 Sep 16;11(9):e0163283. doi: 10.1371/journal.pone.0163283. eCollection 2016.
Venus kinase receptors (VKRs) are invertebrate receptor tyrosine kinases (RTKs) formed by an extracellular Venus Fly Trap (VFT) ligand binding domain associated via a transmembrane domain with an intracellular tyrosine kinase (TK) domain. Schistosoma mansoni VKRs, SmVKR1 and SmVKR2, are both implicated in reproductive activities of the parasite. In this work, we show that the SH2 domain-containing protein SmShb is a partner of the phosphorylated form of SmVKR1. Expression of these proteins in Xenopus oocytes allowed us to demonstrate that the SH2 domain of SmShb interacts with the phosphotyrosine residue (pY979) located in the juxtamembrane region of SmVKR1. This interaction leads to phosphorylation of SmShb on tyrosines and promotes SmVKR1 signaling towards the JNK pathway. SmShb transcripts are expressed in all parasite stages and they were found in ovary and testes of adult worms, suggesting a possible colocalization of SmShb and SmVKR1 proteins. Silencing of SmShb in adult S. mansoni resulted in an accumulation of mature sperm in testes, indicating a possible role of SmShb in gametogenesis.
维纳斯激酶受体（VKRs）是无脊椎动物的受体酪氨酸激酶（RTKs），由一个细胞外捕蝇草（VFT）配体结合结构域通过跨膜结构域与一个细胞内酪氨酸激酶（TK）结构域相连组成。曼氏血吸虫的VKRs，即SmVKR1和SmVKR2，都与该寄生虫的生殖活动有关。在这项研究中，我们发现含SH2结构域的蛋白SmShb是磷酸化形式的SmVKR1的一个结合伙伴。这些蛋白在非洲爪蟾卵母细胞中的表达使我们能够证明SmShb的SH2结构域与位于SmVKR1近膜区域的磷酸酪氨酸残基（pY979）相互作用。这种相互作用导致SmShb的酪氨酸磷酸化，并促进SmVKR1向JNK信号通路的信号传导。SmShb转录本在寄生虫的所有阶段均有表达，并且在成虫的卵巢和睾丸中也有发现，这表明SmShb和SmVKR1蛋白可能共定位。在成年曼氏血吸虫中沉默SmShb会导致睾丸中成熟精子的积累，这表明SmShb在配子发生中可能发挥作用。
