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Interaction of VEGF-C and VEGF-D with neuropilin receptors

PostPosted: Fri Sep 22, 2006 10:21 am
by patoco
Functional interaction of VEGF-C and VEGF-D with neuropilin receptors.

July 2006 Abstract

Karpanen T, Heckman CA, Keskitalo S, Jeltsch M, Ollila H, Neufeld G,
Tamagnone L, Alitalo K.

Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer
Research, Biomedicum Helsinki, P.O.B. 63, FI-00014 University of
Helsinki, Helsinki, Finland.

Lymphatic vascular development is regulated by vascular endothelial
growth factor receptor-3 (VEGFR-3), which is activated by its ligands
VEGF-C and VEGF-D. Neuropilin-2 (NP2), known to be involved in neuronal development, has also been implicated to play a role in
lymphangiogenesis.

We aimed to elucidate the mechanism by which NP2 is involved in
lymphatic endothelial cell signaling. By in vitro binding studies we
found that both VEGF-C and VEGF-D interact with NP2, VEGF-C in a
heparin-independent and VEGF-D in a heparin-dependent manner. We also mapped the domains of VEGF-C and NP2 required for their binding.

The functional importance of the interaction of NP2 with the
lymphangiogenic growth factors was demonstrated by cointernalization of
NP2 along with VEGFR-3 in endocytic vesicles of lymphatic endothelial
cells upon stimulation with VEGF-C or VEGF-D. NP2 also interacted with
VEGFR-3 in coprecipitation studies.

Our results show that NP2 is directly involved in an active signaling
complex with the key regulators of lymphangiogenesis and thus suggest a
mechanism by which NP2 functions in the development of the lymphatic
vasculature.

PMID: 16816121 [PubMed - in process]

http://www.ncbi.nlm.nih.gov/entrez/quer ... etrieve&...

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