title: Detection of ret homodimers in MEN 2A-associated pheochromocytomas.
abstract: 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.
authors.affiliation: Department of Pathology, Nagoya University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Wada
authors.forename: N
authors.initials: N
authors.lastname: Asai
authors.forename: T
authors.initials: T
authors.lastname: Tsuzuki
authors.forename: S
authors.initials: S
authors.lastname: Maruyama
authors.forename: M
authors.initials: M
authors.lastname: Ohiwa
authors.forename: T
authors.initials: T
authors.lastname: Imai
authors.forename: H
authors.initials: H
authors.lastname: Funahashi
authors.forename: H
authors.initials: H
authors.lastname: Takagi
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
mesh_terms: 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
chemical_list: 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