STRUCTURE, EXPRESSION, AND ACTIVITY OF TYRO-3, A NEURAL ADHESION-RELATED RECEPTOR TYROSINE KINASE

We have isolated mouse cDNA clones encoding Tyro 3, a receptor protein -tyrosine kinase (PTK) of the mammalin central nervous system (CNS). E xpression of the Tyro 3 gene is strongly up-regulated in neurons of th e mouse neocortex, cerebellum, and hippocampus after the day of birth, during periods of active synaptogenesis, and high expression is maint ained in the adult CNS. The sequence of Tyro 3 cDNAs predicts a glycop rotein receptor with similarity to neural cell recognition and adhesio n molecules - the extracellular (ligand binding) region of this recept or is composed of two immunoglobulin-related domains followed by two f ibronectin type III repeats. Immunoblot and immunoprecipitation analys es with anti-Tyro 3 antibodies indicate that the 125 kD Tyro 3 protein is abundantly expressed in CNS synaptosomes, and immunohistochemical analysis of cultured hippocampal cells demonstrates that Tyro 3 is a p roduct of neurons. Rat-2 fibroblasts stably transfected with a Tyro 3 expression construct acquire the ability to grow in soft agar, suggest ing that Tyro 3 is potentially oncogenic.