2 FUNCTIONAL FORMS OF VASCULAR ENDOTHELIAL GROWTH-FACTOR-RECEPTOR-2 FLK-1 MESSENGER-RNA ARE EXPRESSED IN NORMAL RAT RETINA

Vascular endothelial growth factor (VEGF) is an important mediator of ocular neovascularization by exerting its endothelial specific mitogen ic effects through high affinity tyrosine kinase receptors. By screeni ng a rat retina cDNA library, we have isolated a clone encoding the fu ll-length prototypic form of the rat VEGF receptor-2/FLk-1, as well as a short form of the mRNA that encodes the complete seven N-terminal i mmunoglobulin-like extracellular ligand-binding domains, transmembrane region, NH2-terminal half of the intracellular kinase domain, and kin ase insert domain but does not encode the COOH-terminal half of the in tracellular kinase domain and carboxyl-terminal region. Both forms of mRNA are detected in rat retina, although the short form is expressed at a lower level. VEGF induced a biphasic increase of cytoplasmic calc ium with both forms in RR 293 transfected cells, indicating that both forms of the VEGF receptor-2/Flk-1 are functional and that the COOH-te rminal half of the intracellular kinase domain and carboxyl region of VEGF receptor-2/Flk-1 are not strictly necessary for either Ligand bin ding or this biological activity.