A protein tyrosine kinase (NYK/FLK-1), bearing all the hallmarks of a growth factor receptor, has been isolated from a cDNA library generated from enriched populations of mouse day 10 embryonic neuroepithelium and from day 18 embryonic colon. Sequence analysis of cDNAs covering the entire coding region of this 5.7 kb mRNA predicted the presence of seven immunoglobulin-like domains in the extracellular region of this molecule. This feature, coupled with the detection of an insert domain bisecting the kinase domain of the predicted protein sequence, places NYK/FLK-1 firmly in the Platelet-derived Growth Factor Receptor-related class of molecules. NYK/FLK-1 is expressed at high levels in adult heart, lung, kidney, brain and skeletal muscle, but is also expressed at lower levels in most other adult tissues. In situ hybridization of day 12.5 embryo sections demonstrated NYK/FLK-1 mRNA expression in endothelial cells lining the dorsal aorta and intervertebral veins. In addition, expression was found in cells lining the capillary plexus which surrounds the developing neuroepithelium, and in the endothelial cells which are found within the embryonic lung, spleen, liver and metanephros.