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| Content Provider | PubMed Central |
|---|---|
| Author | Gagnon, Michael L. Bielenberg, Diane R. Gechtman, Ze'ev Miao, Hua-quan Takashima, Seiji Shay, Soker Michael, Klagsbrun |
| Copyright Year | 2000 |
| Abstract | Neuropilin-1 (NRP1) is a 130-kDa transmembrane receptor for semaphorins, mediators of neuronal guidance, and for vascular endothelial growth factor 165 (VEGF165), an angiogenesis factor. A 2.2-kb truncated NRP1 cDNA was cloned that encodes a 644-aa soluble NRP1 (sNRP1) isoform containing just the a/CUB and b/coagulation factor homology extracellular domains of NRP1. sNRP1 is secreted by cells as a 90-kDa protein that binds VEGF165, but not VEGF121. It inhibits 125I-VEGF165 binding to endothelial and tumor cells and VEGF165-induced tyrosine phosphorylation of KDR in endothelial cells. The 3′ end of sNRP1 cDNA contains a unique, 28-bp intron-derived sequence that is absent in full-length NRP1 cDNA. Using a probe corresponding to this unique sequence, sNRP1 mRNA could be detected by in situ hybridization differentially from full-length NRP1 mRNA, for example, in cells of liver, kidney, skin, and breast. Analysis of blood vessels in situ showed that NRP1, but not sNRP1, was expressed. sNRP1 was functional in vivo. Unlike control tumors, tumors of rat prostate carcinoma cells expressing recombinant sNRP1 were characterized by extensive hemorrhage, damaged vessels, and apoptotic tumor cells. These results demonstrate the existence of a naturally occurring, soluble NRP1 that is expressed differently from intact NRP1 and that appears to be a VEGF165 antagonist. |
| Related Links | http://dx.doi.org/10.1073/pnas.040337597 |
| Ending Page | 2578 |
| Page Count | 6 |
| Starting Page | 2573 |
| File Format | |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 6 |
| Volume Number | 97 |
| Language | English |
| Publisher | The National Academy of Sciences |
| Publisher Date | 2000-03-14 |
| Access Restriction | Open |
| Rights Holder | The National Academy of Sciences |
| Subject Keyword | General Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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