Neuropilin-1 is a receptor for transforming growth factor beta-1, activates its latent form, and promotes regulatory T cell activity.
Neuropilin-1 is a receptor for transforming growth factor beta-1, activates its latent form, and promotes regulatory T cell activity.
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DOI：
10.1189/jlb.0208090
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发表时间：
2008-07
影响因子：
5.5
通讯作者：
Prud'homme, Gerald J.
中科院分区：
文献类型：
--
作者：
Glinka, Yelena;Prud'homme, Gerald J.
神经纤毛蛋白-1（Nrp 1）是一种多功能蛋白质，主要被鉴定为3类信号蛋白和血管内皮生长因子（VEGF）家族成员的受体，但它能够进行其他相互作用。它是调节性T细胞（Tr）的标志物，通常携带Nrp 1和潜伏相关肽（LRP）-TGF-β1（潜伏形式）。信号转导TGF-β1受体仅结合活性TGF-β1，我们假设Nrp 1结合潜伏形式。事实上，我们发现Nrp 1是潜在和活性TGF-β1的高亲和力受体。游离TGF-β1、LAP-TGF-β1和活性TGF-β1均与VEGF 165竞争结合Nrp 1。VEGF具有一个类似于VEGF的碱性、富含精氨酸的C-末端基序，以及与Nrp 1的b1结构域结合的肽。一个C-末端的Nrp肽（QSSRHRR）与Nrp 1结合并抑制VEGF和LAP-TGF-β1的结合。我们还分析了Nrp 1/LAP-TGF-β1共表达对T细胞功能的影响。与Nrp 1-细胞相比，分选的Nrp 1 + T细胞具有更大的捕获LAP-TGF-β1的能力。分选的Nrp 1- T细胞捕获可溶性Nrp 1-Fc，这增加了它们捕获LAP-TGF-β1的能力。Nrp 1-Fc/LAP-TGF-β1包被的CD 4 + CD 25-Nrp 1- T细胞获得了较强的Tr活性。此外，LAP-TGF-β被Nrp 1-Fc激活，也被Nrp 1的b2结构域的肽（RKFK;类似于血小板反应蛋白-1肽）激活。表达Nrp 1的乳腺癌细胞也以Nrp 1依赖性方式捕获并激活LAP-TGF-β1。因此，Nrp 1是TGF-β1的受体，激活其潜伏形式，并与Tr活性和肿瘤生物学相关。
Neuropilin-1 (Nrp1) is a multifunctional protein, identified principally as a receptor for the class 3 semaphorins and members of the vascular endothelial growth factor (VEGF) family, but it is capable of other interactions. It is a marker of regulatory T cells (Tr), which often carry Nrp1 and latency-associated peptide (LAP)-TGF-β1 (the latent form). The signaling TGF-β1 receptors bind only active TGF-β1, and we hypothesized that Nrp1 binds the latent form. Indeed, we found that Nrp1 is a high-affinity receptor for latent and active TGF-β1. Free LAP, LAP-TGF-β1, and active TGF-β1 all competed with VEGF165 for binding to Nrp1. LAP has a basic, arginine-rich C-terminal motif similar to VEGF and peptides that bind to the b1 domain of Nrp1. A C-terminal LAP peptide (QSSRHRR) bound to Nrp1 and inhibited the binding of VEGF and LAP-TGF-β1. We also analyzed the effects of Nrp1/LAP-TGF-β1 coexpression on T cell function. Compared with Nrp1– cells, sorted Nrp1+ T cells had a much greater capacity to capture LAP-TGF-β1. Sorted Nrp1– T cells captured soluble Nrp1-Fc, and this increased their ability to capture LAP-TGF-β1. Conventional CD4+CD25–Nrp1– T cells coated with Nrp1-Fc/LAP-TGF-β1 acquired strong Tr activity. Moreover, LAP-TGF-β was activated by Nrp1-Fc and also by a peptide of the b2 domain of Nrp1 (RKFK; similar to a thrombospondin-1 peptide). Breast cancer cells, which express Nrp1, also captured and activated LAP-TGF-β1 in a Nrp1-dependent manner. Thus, Nrp1 is a receptor for TGF-β1, activates its latent form, and is relevant to Tr activity and tumor biology.
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DOI：
10.1083/jcb.148.6.1283
发表时间：
2000-03-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Shimizu M;Murakami Y;Suto F;Fujisawa H
通讯作者：
Fujisawa H
影响因子：
11.2
作者：
Matsushita, Arikira;Gotze, Tobias;Korc, Murray
通讯作者：
Korc, Murray
影响因子：
20.3
作者：
Sulpice, Eric;Plouet, Jean;Merkulova-Rainon, Tatyana
通讯作者：
Merkulova-Rainon, Tatyana
影响因子：
4.8
作者：
SCHULTZCHERRY, S;CHEN, H;MURPHYULLRICH, JE
通讯作者：
MURPHYULLRICH, JE
影响因子：
64.8
作者：
Travis, Mark A.;Reizis, Boris;Sheppard, Dean
通讯作者：
Sheppard, Dean