We report the nucleotide sequence of the mouse ret proto-oncogene (proto-ret) and the deduced amino acid sequence. It encodes a transmembrane tyrosine kinase of 1115 amino acids that shows 83% homology with the human proto-Ret protein. The amino acid sequence revealed that the structures of the extracellular domain as well as the tyrosine kinase domain are similar in human and mouse proto-Ret proteins. Interestingly, the extracellular domains of both human and mouse proto-Ret proteins contain a cadherin-related sequence that is known to be important for Ca(2+)-dependent homophilic binding of the cadherins. When we examined transcription of the proto-ret gene in a variety of mouse tissues, it was detected in lymph nodes of C3H/HeJ-gld/gld mice and in normal mouse spinal cord. Furthermore, its transcription was found in the Neuro-2a mouse neuroblastoma cell line but not in 13 other rodent cell lines surveyed. Western blot analysis showed that proto-Ret proteins are expressed as 140-kDa and 160-kDa glycoproteins in Neuro-2a cells.