The Ret proto-oncogene is structurally related to the growing family of
tyrosine kinase transmembrane receptors and is involved in GDNF signaling.
By alternative splicing, two isoforms of the Ret proto-oncogene product are
generated. The isoforms differ from each other by having either 9 or 51 carboxy
terminal amino acids. The Ret gene products include two glycosylated
proteins in tunicamycin treated cells, a non-glycosylated protein consistent
with the predicted Ret molecular weight based on sequence analysis. Tumorspecific
rearrangements of the Ret proto-oncogene have been identified in
papillary thyroid carcinomas leading to the formation of different transforming
fusion proteins sharing the tyrosine kinase domain of Ret. In contrast to
the Ret proto-oncogene, the rearranged forms are constitutively phosphorylated
on tyrosine and are translocated from the membrane to the cytoplasm.