Identification of two novel altematively spliced Neuropilin-1 isoforms

被引:70
|
作者
Cackowski, FC
Xu, L
Hu, B
Cheng, SY
机构
[1] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Res Pavil, Pittsburgh, PA 15213 USA
[2] Univ Pittsburgh, Dept Pathol, Hillman Canc Ctr, Res Pavil, Pittsburgh, PA 15213 USA
[3] Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA
[4] Univ Pittsburgh, Dept Med, Hillman Canc Ctr, Res Pavil, Pittsburgh, PA 15213 USA
关键词
neuropilin-1; VEGF receptor; angiogenesis; cell migration;
D O I
10.1016/j.ygeno.2004.02.001
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Neuropilin-1 (NRP1) is a coreceptor to a tyrosine kinase receptor for both the vascular endothelial growth factor (VEGF) family and semaphorin (Sema) family members. NRP1 plays versatile roles in angiogenesis, axon guidance, cell survival, migration, and invasion. NRP1 contains three distinct extracellular domains, a1a2, b1b2, and c. We report here the identification of two novel soluble human NRP1 isoforms, which we named s(III)NRP1 and s(IV)NRP1. These soluble NRP1 isoforms were generated by alternative splicing of the NRP1 gene, a common regulatory mechanism occurring in cell surface receptor families. Both s(III)NRP1 and s(IV)NRP1 contain a1a2 and b1b2 domains, but no c domain, and the rest of the NRP1 sequence. Additionally, s(III)NRP1 is missing 48 amino acids within the C-terminus of the b2 domain. Both s(III)NRP1 and s(IV)NRP1 are expressed in human cancerous and normal tissues. These molecules are capable of binding to VEGF(165) and Sema3A. Furthermore, recombinant s(III)NRP1 and s(IV)NRP1 proteins inhibit NRP1-mediated MDA-MB-231 breast cancer cell migration. These results indicate the multiple levels of regulation in NRP1 function and suggest that these two novel NRP1 isoforms are useful antagonists for NRP1-mediated cellular activities. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:82 / 94
页数:13
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