The interaction of Neuropilin-1 and Neuropilin-2 with tyrosine-kinase receptors for VEGF.
The Neuropilin-1 (NRP1) and Neuropilin-2 (NRP2) receptors were initially described as receptors for axon guidance factors belonging to the class-3 Semaphorin sub-family. Subsequently, it was found the Neuropilins also function as receptors for some forms of vascular endothelial growth factor (VEGF). VEGF165 binds to both NRP1 and to NRP2 but VEGF121, does not bind to either of these receptors. VEGF145 on the other hand, binds to NRP2 but not to NRP1. Additional VEGF family members such as the heparin binding form of placenta growth factor (PlGF-2) and VEGF-B bind to NRP1, and it was also shown that both PlGF-2 and VEGF-C bind to NRP2. The intracellular domains of the Neuropilins are short, and do not suffice for independent transduction of biological signals subsequent to Semaphorin or VEGF binding. It was shown that both Neuropilins can form complexes with receptors belonging to the Plexin family, and that such Plexin/Neuropilin complexes are able to transduce signals following the binding of class-3 Semaphorins to Neuropilins. The VEGF165 induced proliferation and migration of cells that express the VEGF tyrosine-kinase receptor VEGFR2 is enhanced in the presence of NRP1, suggesting that Neuropilins may also form complexes with VEGF tyrosine-kinase receptors such as VEGFR2. However, it is not yet clear whether VEGFR2 and NRPI form complexes and contrasting results have been reported with regard to this issue. In contrast, it was recently reported by two laboratories that Neuropilins can form complexes with the second tyrosine-kinase receptor of VEGF, VEGFR1. However, the biological function of these complexes is still unclear.
Neufeld
Gera
G
Department of Biology, Technion, Israel Institute of Technology, Haifa, 32000, Israel. gera@tx.technion.ac.il
Kessler
Ofra
O
Herzog
Yael
Y
D000818:Animals; D006801:Humans; D039942:Neuropilin-1 / Q000502:physiology*; D039943:Neuropilin-2 / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D040281:Vascular Endothelial Growth Factor Receptor-1
D039943:Neuropilin-2; D039942:Neuropilin-1; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1