Crosstalk between VEGF-A/VEGFR2 and GDNF/RET signaling pathways
- Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Ave., Forchheimer Bldg., Room 708, Bronx, NY 10461 (United States) and Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Forchheimer Bldg., Room 708, Bronx, NY 10461 (United States)
- Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Ave., Forchheimer Bldg., Room 708, Bronx, NY 10461 (United States)
Vascular endothelial growth factor (VEGF-A) plays multiple roles in kidney development: stimulates cell proliferation, survival, tubulogenesis, and branching morphogenesis. However, the mechanism that mediates VEGF-A induced ureteric bud branching is unclear. Glial-derived neurotrophic factor (GDNF) signaling through tyrosine kinase c-RET is the major regulator of ureteric bud branching. Here we examined whether VEGF-A regulates RET signaling. We determined that ureteric bud-derived cells express the main VEGF-A signaling receptor, VEGFR2 and RET, by RT-PCR, immunoblotting, and immunocytochemistry. We show that the VEGF-A isoform VEGF{sub 165} induces RET-tyr{sup 1062} phosphorylation in addition to VEGFR2 autophosphorylation, that VEGF{sub 165} and GDNF have additive effects on RET-tyr{sup 1062} phosphorylation, and that VEGFR2 and RET co-immunoprecipitate. Functionally, VEGF{sub 165} induces ureteric bud cell proliferation and branching morphogenesis. Similarly, in embryonic kidney explants VEGF{sub 165} induces RET-tyr{sup 1062} phosphorylation and upregulates GDNF. These findings provide evidence for a novel cooperative interaction between VEGFR2 and RET that mediates VEGF-A functions in ureteric bud cells.
- OSTI ID:
- 20991405
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 358, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2007.04.146; PII: S0006-291X(07)00841-8; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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