c-ret and signal transduction

DURING THE PAST few years, much effort has been made to understand the function of the proto-oncogene c-ret, a putative receptor tyrosine kinase. Mice homozygous for a null c-ret allele showed severe kidney abnormalities and lacked enteric neurons, indicating that c-ret is involved in the development and differentiation of the kidney and enteric nervous system. The c-ret proto-oncogene can be activated by either DNA rearrangement, in which its tyrosine kinase domain is fused to other genes, or by point mutations in specific domains. Point mutations in c-ret have been linked to several inherited human cancer syndromes, including multiple endocrine neoplasia type 2A and 2B and familial medullary thyroid carcinoma. These recombinations and point mutations may interfere with the function of normal c-ret in a signaling pathway, which subsequently results in cellular transformation.