| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
E-mail contact: gera@tx.technion.ac.il
The neuropilin-1 (np1) receptor binds the 165 amino-acid form of vascular endothelial growth factor165 (VEGF165) and functions as an enhancer that potentiates VEGF165 signaling via the VEGFR-2 tyrosine-kinase receptor. To study the mechanism by which neuropilins potentiate VEGF activity we produced a VEGF165 mutant (VEGF165KF) that binds to neuropilins but displays a much lower affinity toward VEGFR-1 and VEGFR-2. VEGF165KF failed to induce VEGFR-2 phosphorylation in cells lacking neuropilins. However, in the presence of np1, VEGF165KF bound weakly to VEGFR-2, induced VEGFR-2 phosphorylation, and activated ERK1/2. Interestingly, VEGF165KF did not promote formation of VEGFR-2/np1 complexes nor did high concentrations of VEGF165KF inhibit VEGF165 induced formation of such complexes, suggesting that VEGF165 does not stabilize VEGFR-2/np1 complexes by forming bridges spanning VEGFR-2 and np1. VEGF121 is a VEGF form that does not bind to neuropilins. Surprisingly, both np1 and neuropilin-2 (np2) enhanced VEGF121-induced phosphorylation of VEGFR-2 and VEGF121-induced proliferation of endothelial cells. The enhancement of VEGF121 activity by np1 was accompanied by a 10-fold increase in binding affinity to VEGFR-2 and was not associated with the formation of new VEGFR-2/np1 complexes. These observations suggest that neuropilins enhance the activity of VEGF forms that do not bind to neuropilins, indicate that np2 is a functional VEGF receptor, and imply that spontaneously formed VEGFR-2/np1 complexes suffice for efficient neuropilin mediated enhancement of VEGF activity.--Shraga-Heled, N., Kessler, O., Prahst, C., Kroll, J., Augustin, H., Neufeld, G. Neuropilin-1 and neuropilin-2 enhance VEGF121 stimulated signal transduction by the VEGFR-2 receptor.
Related Articles
This article has been cited by other articles:
|
|
 |
|
  C. Prahst, M. Heroult, A. A. Lanahan, N. Uziel, O. Kessler, N. Shraga-Heled, M. Simons, G. Neufeld, and H. G. Augustin Neuropilin-1-VEGFR-2 Complexing Requires the PDZ-binding Domain of Neuropilin-1 J. Biol. Chem., September 12, 2008; 283(37): 25110 - 25114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Cebe-Suarez, F. S. Grunewald, R. Jaussi, X. Li, L. Claesson-Welsh, D. Spillmann, A. A. Mercer, A. E. Prota, and K. Ballmer-Hofer Orf virus VEGF-E NZ2 promotes paracellular NRP-1/VEGFR-2 coreceptor assembly via the peptide RPPR FASEB J, August 1, 2008; 22(8): 3078 - 3086. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Wang, P. W. Faloon, Z. Tan, Y. Lv, P. Zhang, Y. Ge, H. Deng, and J.-W. Xiong Mouse lysocardiolipin acyltransferase controls the development of hematopoietic and endothelial lineages during in vitro embryonic stem-cell differentiation Blood, November 15, 2007; 110(10): 3601 - 3609. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Dai and A.B.M. Rabie VEGF: an Essential Mediator of Both Angiogenesis and Endochondral Ossification J. Dent. Res., October 1, 2007; 86(10): 937 - 950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Guttmann-Raviv, N. Shraga-Heled, A. Varshavsky, C. Guimaraes-Sternberg, O. Kessler, and G. Neufeld Semaphorin-3A and Semaphorin-3F Work Together to Repel Endothelial Cells and to Inhibit Their Survival by Induction of Apoptosis J. Biol. Chem., September 7, 2007; 282(36): 26294 - 26305. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
