Identification of two novel alternatively spliced Neuropilin-1 isoforms

Frank C. Cackowski, Li Xu, Bo Hu*, Shi Yuan Cheng

*Corresponding author for this work

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

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 sIIINRP1 and s IVNRP1. These soluble NRP1 isoforms were generated by alternative splicing of the NRP1 gene, a common regulatory mechanism occurring in cell surface receptor families. Both sIIINRP1 and sIVNRP1 contain a1a2 and b1b2 domains, but no c domain, and the rest of the NRP1 sequence. Additionally, sIIINRP1 is missing 48 amino acids within the C-terminus of the b2 domain. Both sIIINRP1 and sIVNRP1 are expressed in human cancerous and normal tissues. These molecules are capable of binding to VEGF165 and Sema3A. Furthermore, recombinant s IIINRP1 and sIVNRP1 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.

Original languageEnglish (US)
Pages (from-to)82-94
Number of pages13
JournalGenomics
Volume84
Issue number1
DOIs
StatePublished - Jul 1 2004

Fingerprint

Neuropilin-1
Protein Isoforms
Cell Movement
Semaphorin-3A
Semaphorins
Alternative Splicing
Receptor Protein-Tyrosine Kinases
Cell Surface Receptors
Vascular Endothelial Growth Factor A
Cell Survival

Keywords

  • Angiogenesis
  • Cell migration
  • Neuropilin-1
  • VEGF receptor

ASJC Scopus subject areas

  • Genetics

Cite this

Cackowski, Frank C. ; Xu, Li ; Hu, Bo ; Cheng, Shi Yuan. / Identification of two novel alternatively spliced Neuropilin-1 isoforms. In: Genomics. 2004 ; Vol. 84, No. 1. pp. 82-94.
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Identification of two novel alternatively spliced Neuropilin-1 isoforms. / Cackowski, Frank C.; Xu, Li; Hu, Bo; Cheng, Shi Yuan.

In: Genomics, Vol. 84, No. 1, 01.07.2004, p. 82-94.

Research output: Contribution to journalArticle

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