Detection of ret homodimers in MEN 2A-associated pheochromocytomas.
Using transfection of NIH 3T3 cells, we have recently demonstrated that multiple endocrine neoplasia (MEN) 2A mutations activate the c-Ret protein by inducing its disulfide-linked homodimerization on the cell surface. To investigate whether the homodimers are present in original tumors, the expression of the c-Ret protein was analyzed in eight sporadic and two MEN 2A-associated pheochromocytomas, the latter two of which contained mutations in cysteine 618 or 634 of Ret. The c-Ret protein was expressed at variable levels in all pheochromocytomas examined. By labeling the c-Ret protein immunoprecipitated from tumor tissues with [gamma-32P]ATP in vitro, its homodimers were detected in pheochromocytomas from MEN 2A patients but not in a sporadic tumor. This result represents the first demonstration of Ret homodimers in original tumors.
Wada
M
M
Department of Pathology, Nagoya University School of Medicine, Japan.
Asai
N
N
Tsuzuki
T
T
Maruyama
S
S
Ohiwa
M
M
Imai
T
T
Funahashi
H
H
Takagi
H
H
Takahashi
M
M
D029721:Drosophila Proteins; D006801:Humans; D046911:Macromolecular Substances; D008970:Molecular Weight; D018813:Multiple Endocrine Neoplasia Type 2a / Q000737:chemistry*; D009154:Mutation; D010673:Pheochromocytoma / Q000737:chemistry*; D017354:Point Mutation; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry* / Q000235:genetics
D029721:Drosophila Proteins; D046911:Macromolecular Substances; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila