Characterization of a multicomponent receptor for GDNF

Post-transcriptional silencing of RET occurs, but is not required, during raf-1 mediated differentiation of medullary thyroid carcinoma cells

“…Activating mutations in the RET protooncogene have been described in all forms of MTC. RET is a receptor tyrosine kinase (Takahashi and Cooper, 1987) which interacts with glial cell linederived neurotrophic factor (GDNF) (Durbec et al, 1996;Jing et al, 1996;Treanor et al, 1996;Trupp et al, 1996) and a newly described, related protein, neurturin (NTN) (Buj-Bello et al, 1997;Creedon et al, 1997;Klein et al, 1997), via coreceptors GDNFR-a and NTNR-a respectively. Commonly, mutations in extracellular cysteine residues encoded by exons 10 and 11 of RET are associated with two inherited MTC syndromes, familial medullary thyroid carcinoma (FMTC) and multiple endocrine neoplasia type 2A (MEN 2A) (Donis-Keller et al, 1993;Mulligan et al, 1993).…”

Genomic structure and chromosomal localization of the human GDNFR-α gene

“…No other structural motifs are identi®ed. Interestingly, an insertion of ®ve amino acids, reported in some studies (Jing et al, 1996;Treanor et al, 1996), was not found in this analysis. These amino acids are predicted to lie at the boundary of exons 3 and 4.…”

“…It shows little homology to other known protein families although it contains 30 cysteine residues spaced similarly to those in the cytokine receptors (Treanor et al, 1996). We have shown that GDNFR-a comprises 9 coding exons ranging in size from 40 ± 337 bp.…”

“…The human GDNFR-a gene has recently been isolated and encodes an open reading frame of H60 of 465 amino acids with a signal peptide at the amino terminus, a stretch of 20 ± 23 hydrophobic amino acids at the carboxy terminus and three possible glycosylation sites (Jing et al, 1996;Treanor et al, 1996;Sanicola et al, 1997). Although GDNFR-a has no strong homologies to any other receptor, it does encode 30 cysteine residues with similar spacing and arrangement to those found in many cytokine receptors (Treanor et al, 1996;Sanicola et al, 1997). The absence of any C-terminal hydrophilic sequence and the presence of a cluster of small amino acids that de®ne a site for the GPI-linkage suggest that GDNFRa is a glycolipid-linked extracellular protein attached to the cell membrane, without an intracellular signalling domain.…”

Sex difference in immunostaining of RET in the adult mouse kidney

“…The phenotype is similar to that of mice homozygous for a null mutation in glial-cell-line-derived neurotrophic factor, GDNF Pichel et al, 1996;Sa nchez et al, 1996). Concurrently, binding of GDNF through GDNFR-a to RET was shown biochemically, which resulted in autophosphorylation of RET (Jing et al, 1996;Treanor et al, 1996).…”