The fms-like tyrosine kinase (Flt) is a transmembrane receptor in the tyrosine kinase family. Expression of flt complementary DNA in COS cells conferred specific, high-affinity binding of vascular endothelial growth factor, also known as vascular permeability factor (VEGF-VPF), a factor that induces vascular permeability when injected in the guinea pig skin and stimulates endothelial cell proliferation. Expression of Flt in Xenopus laevis oocytes caused the oocytes to release calcium in response to VEGF-VPF. These findings show that flt encodes a receptor for VEGF-VPF.

The primary structure of the receptor for platelet-derived growth factor (PDGF), determined by means of cloning a cDNA that encodes the murine pre-PDGF receptor, is closely related to that of the v-kit oncogene product and the receptor for macrophage colony stimulating factor (CSF-1). Common structural features include the presence of long sequences that interrupt the tyrosine-specific protein kinase domains of each molecule. The PDGF and CSF-1 receptors also share a characteristic distribution of extracellular cysteine residues. Ubiquitin is covalently bound to the purified PDGF receptor, the human gene for which is on chromosome 5.

Src homology 2 (SH2) domains bind specifically to tyrosine-phosphorylated proteins that participate in signaling by growth factors and oncogenes. A protein domain was identified that bound specifically to the tyrosine-phosphorylated form of its target protein but differs from known SH2 sequences. Phosphotyrosine-binding (PTB) domains were found in two proteins: SHC, a protein implicated in signaling through Ras; and SCK, encoded by a previously uncharacterized gene. The PTB domain of SHC specifically bound to a tyrosine-phosphorylated 145-kilodalton protein. PTB domains are an alternative to SH2 domains for specifically recruiting tyrosine-phosphorylated proteins into signaling complexes and are likely to take part in signaling by many growth factors.

Vascular end lgwt factor (VEGF) b a polyetide mitogen that mulats the growth of endotlil clsin vigro and promotesthe growth ofblood vess in vivo. We have recetly shown that the ths-like receptor tyrosne kinae (flt) Is a receptor for VEGF. Here we used in siu hybrdzation to show that, In adult mouse tissues, the pattern offltexp-esslon was consstent with lo t io n endothe . We also show thatfkwas expsed endothellum during neovacularizton of heai skin wounds and during eady vascular devdopment In mose embyos. Moreover,ft was expsed In populatons of embyoniccels from which endotellIum Is derived such as early yolk sac mesenchyme. The epreson offt In the endotelium of both developing and mature blood vessels that VEGF might rgulate endothelal dierentition, blod vessel growth, and vasular repair.