PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 20235151-3 2010 Arsenic further activated RET-MEN2A kinase, which was already 3- to 10-fold augmented by genetic mutation compared with c-RET kinase activity, with promotion of disulfide bond-mediated dimerization of RET-MEN2A protein (superactivation). Disulfides 161-170 ret proto-oncogene Homo sapiens 205-210 20235151-2 2010 Arsenic activated c-RET kinase with promotion of disulfide bond-mediated dimerization of c-RET protein. Disulfides 49-58 ret proto-oncogene Homo sapiens 91-94 20235151-4 2010 Arsenic also increased extracellular domain-deleted RET-PTC1 kinase activity with promotion of disulfide bond-mediated dimerization of RET-PTC1 protein. Disulfides 95-104 ret proto-oncogene Homo sapiens 135-138 16732321-1 2006 In patients with medullary thyroid carcinoma (MTC) and type 2A multiple endocrine neoplasia (MEN2A), mutations of cysteine residues in the extracellular juxtamembrane region of the RET receptor tyrosine kinase cause the formation of covalent receptor dimers linked by intermolecular disulfide bonds between unpaired cysteines, followed by oncogenic activation of the RET kinase. Disulfides 283-292 ret proto-oncogene Homo sapiens 93-98 16732321-1 2006 In patients with medullary thyroid carcinoma (MTC) and type 2A multiple endocrine neoplasia (MEN2A), mutations of cysteine residues in the extracellular juxtamembrane region of the RET receptor tyrosine kinase cause the formation of covalent receptor dimers linked by intermolecular disulfide bonds between unpaired cysteines, followed by oncogenic activation of the RET kinase. Disulfides 283-292 ret proto-oncogene Homo sapiens 181-184 14715928-4 2004 These mutations constitutively activate RET due to aberrant disulfide homodimerization and diminish the level of RET at the plasma membrane. Disulfides 60-69 ret proto-oncogene Homo sapiens 40-43 11213488-3 2000 We found that small proportions of c-Ret and Ret-MEN2B and a large proportion of MEN2A were dimerized due to disulfide bonds and that high kinase activity resided in these fractions. Disulfides 109-118 ret proto-oncogene Homo sapiens 45-48 11491658-0 2001 Osmotic stress-mediated activation of RET kinases involves intracellular disulfide-bonded dimer formation. Disulfides 73-82 ret proto-oncogene Homo sapiens 38-41 11491658-2 2001 A few percentage of RET proteins normally formed disulfide-bonded dimers in the cell, and osmotic stress promoted formation of these dimers. Disulfides 49-58 ret proto-oncogene Homo sapiens 20-23 11491658-4 2001 Osmotic stress also promoted activation and disulfide-bonded dimerization of the extracellular domain-depleted mutant RET (RET-PTC-1), suggesting that the target amino acid(s) for dimerization is located intracellularly rather than in the cysteine-rich region of the extracellular domain. Disulfides 44-53 ret proto-oncogene Homo sapiens 118-121 11491658-4 2001 Osmotic stress also promoted activation and disulfide-bonded dimerization of the extracellular domain-depleted mutant RET (RET-PTC-1), suggesting that the target amino acid(s) for dimerization is located intracellularly rather than in the cysteine-rich region of the extracellular domain. Disulfides 44-53 ret proto-oncogene Homo sapiens 123-126 11121408-7 2001 Interestingly, LAR expression significantly decreased the levels of disulfide-linked RET-MEN2A dimerization. Disulfides 68-77 ret proto-oncogene Homo sapiens 85-88 11121408-7 2001 Interestingly, LAR expression significantly decreased the levels of disulfide-linked RET-MEN2A dimerization. Disulfides 68-77 ret proto-oncogene Homo sapiens 89-94 11213488-3 2000 We found that small proportions of c-Ret and Ret-MEN2B and a large proportion of MEN2A were dimerized due to disulfide bonds and that high kinase activity resided in these fractions. Disulfides 109-118 ret proto-oncogene Homo sapiens 49-54 11213488-3 2000 We found that small proportions of c-Ret and Ret-MEN2B and a large proportion of MEN2A were dimerized due to disulfide bonds and that high kinase activity resided in these fractions. Disulfides 109-118 ret proto-oncogene Homo sapiens 81-86 11213488-4 2000 The UV-induced activation of c-Ret and superactivation of Ret-MEN2A and Ret-MEN2B were then shown to be closely associated with promotion of the disulfide bond-mediated dimerization of the Ret proteins. Disulfides 145-154 ret proto-oncogene Homo sapiens 31-34 11213488-4 2000 The UV-induced activation of c-Ret and superactivation of Ret-MEN2A and Ret-MEN2B were then shown to be closely associated with promotion of the disulfide bond-mediated dimerization of the Ret proteins. Disulfides 145-154 ret proto-oncogene Homo sapiens 58-61 11213488-4 2000 The UV-induced activation of c-Ret and superactivation of Ret-MEN2A and Ret-MEN2B were then shown to be closely associated with promotion of the disulfide bond-mediated dimerization of the Ret proteins. Disulfides 145-154 ret proto-oncogene Homo sapiens 62-67 11213488-4 2000 The UV-induced activation of c-Ret and superactivation of Ret-MEN2A and Ret-MEN2B were then shown to be closely associated with promotion of the disulfide bond-mediated dimerization of the Ret proteins. Disulfides 145-154 ret proto-oncogene Homo sapiens 58-61 11213488-4 2000 The UV-induced activation of c-Ret and superactivation of Ret-MEN2A and Ret-MEN2B were then shown to be closely associated with promotion of the disulfide bond-mediated dimerization of the Ret proteins. Disulfides 145-154 ret proto-oncogene Homo sapiens 76-81 11213488-4 2000 The UV-induced activation of c-Ret and superactivation of Ret-MEN2A and Ret-MEN2B were then shown to be closely associated with promotion of the disulfide bond-mediated dimerization of the Ret proteins. Disulfides 145-154 ret proto-oncogene Homo sapiens 58-61 10637293-6 2000 We found that UV irradiation promotes the disulfide bond-mediated dimerization of the Ret proteins, in close association with activation and superactivation of Ret kinases. Disulfides 42-51 ret proto-oncogene Homo sapiens 86-89 10637293-4 2000 Before UV irradiation, small percentages of c-Ret (3-4%) and Ret-MEN2B (1-2%) and large percentages of Ret-MEN2A (30-40%) were dimerized through disulfide bonds. Disulfides 145-154 ret proto-oncogene Homo sapiens 107-112 10637293-5 2000 These dimerized Ret proteins were preferentially autophosphorylated, suggesting a close relation between up-regulated kinase activity and disulfide bond-mediated dimerization of Ret proteins. Disulfides 138-147 ret proto-oncogene Homo sapiens 16-19 10637293-5 2000 These dimerized Ret proteins were preferentially autophosphorylated, suggesting a close relation between up-regulated kinase activity and disulfide bond-mediated dimerization of Ret proteins. Disulfides 138-147 ret proto-oncogene Homo sapiens 178-181 10637293-6 2000 We found that UV irradiation promotes the disulfide bond-mediated dimerization of the Ret proteins, in close association with activation and superactivation of Ret kinases. Disulfides 42-51 ret proto-oncogene Homo sapiens 160-163 9620546-2 1998 In MEN2A mutations affecting cysteine residues in the extracellular domain of the receptor cause constitutive activation of the tyrosine kinase by the formation of disulfide-bonded homodimers. Disulfides 164-173 ret proto-oncogene Homo sapiens 3-8 10049754-4 1999 The D631Y mutation activated Ret by inducing its disulfide-linked dimerization in the transfectant as observed for multiple endocrine neoplasia (MEN) 2A mutations at cysteine 609, 611, 618, 620, 630, or 634. Disulfides 49-58 ret proto-oncogene Homo sapiens 29-32 10049754-4 1999 The D631Y mutation activated Ret by inducing its disulfide-linked dimerization in the transfectant as observed for multiple endocrine neoplasia (MEN) 2A mutations at cysteine 609, 611, 618, 620, 630, or 634. Disulfides 49-58 ret proto-oncogene Homo sapiens 124-152 10049754-5 1999 Further mutation analysis suggested that cysteine 630 or 634 could be involved in the disulfide-linked Ret dimerization induced by the D631Y mutation. Disulfides 86-95 ret proto-oncogene Homo sapiens 103-106 9879991-7 1998 We now report that each mutation induces a constitutive catalytic activity due to the aberrant disulfide homodimerization of RET. Disulfides 95-104 ret proto-oncogene Homo sapiens 125-128 9502784-8 1998 Finally, the C609W HSCR mutation exerts a dual effect on RET since it leads to a decrease of the receptor at the cell surface and converted RET51 into a constitutively activated kinase due to the formation of disulfide-linked homodimers. Disulfides 209-218 ret proto-oncogene Homo sapiens 57-60 9502784-8 1998 Finally, the C609W HSCR mutation exerts a dual effect on RET since it leads to a decrease of the receptor at the cell surface and converted RET51 into a constitutively activated kinase due to the formation of disulfide-linked homodimers. Disulfides 209-218 ret proto-oncogene Homo sapiens 140-145 9242375-3 1997 The majority of MEN2A and FMTC mutations are clustered in the extra-cellular cysteine-rich domain and result in constitutive activation of the tyrosine kinase through the formation of disulfide-bonded RET homodimers. Disulfides 184-193 ret proto-oncogene Homo sapiens 16-21 10027003-4 1998 MEN2A mutations involve cysteine residues present in the Ret extracellular domain and induce disulfide-linked Ret dimerization on the cell surface. Disulfides 93-102 ret proto-oncogene Homo sapiens 0-5 10027003-4 1998 MEN2A mutations involve cysteine residues present in the Ret extracellular domain and induce disulfide-linked Ret dimerization on the cell surface. Disulfides 93-102 ret proto-oncogene Homo sapiens 57-60 10027003-4 1998 MEN2A mutations involve cysteine residues present in the Ret extracellular domain and induce disulfide-linked Ret dimerization on the cell surface. Disulfides 93-102 ret proto-oncogene Homo sapiens 110-113 9242375-3 1997 The majority of MEN2A and FMTC mutations are clustered in the extra-cellular cysteine-rich domain and result in constitutive activation of the tyrosine kinase through the formation of disulfide-bonded RET homodimers. Disulfides 184-193 ret proto-oncogene Homo sapiens 201-204 7532281-3 1995 The 170-kDa Ret protein present on the cell surface of transformed cells was highly phosphorylated on tyrosine and formed disulfide-linked homodimers. Disulfides 122-131 ret proto-oncogene Homo sapiens 12-15 9012462-6 1997 We have reported previously that mutations of Cys-634 constitutively activate the RET transforming potential by causing a disulfide bridge-mediated homodimerization. Disulfides 122-131 ret proto-oncogene Homo sapiens 82-85 8561803-1 1996 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. Disulfides 163-172 ret proto-oncogene Homo sapiens 135-138 26780347-6 2016 Moreover, we have reported that three kinds of oxidative stress, ultraviolet light-induced stress, osmotic stress and arsenic-induced stress, modulate kinase activity of RET-PTC1 without an extracellular domain as well as c-RET by conformational change of RET protein (dimerization) via disulfide bond formation. Disulfides 287-296 ret proto-oncogene Homo sapiens 170-173 32064171-5 2020 We have previously reported that a conserved cysteine in the MXXCW motif of RET is crucial to the disulfide-bonded dimerization-linked activation of RET kinases. Disulfides 98-107 ret proto-oncogene Homo sapiens 76-79 32064171-5 2020 We have previously reported that a conserved cysteine in the MXXCW motif of RET is crucial to the disulfide-bonded dimerization-linked activation of RET kinases. Disulfides 98-107 ret proto-oncogene Homo sapiens 149-152 32064171-6 2020 Reagents which bind to this cysteine may inhibit the activity of RET kinases through disulfide-bond mediated dimerization. Disulfides 85-94 ret proto-oncogene Homo sapiens 65-68 8573606-3 1995 MEN 2A mutations involved cysteine residues in the extracellular domain and induced disulfide-linked homodimerization of the Ret protein on the cell surface, leading to activation of its intrinsic tyrosine kinase. Disulfides 84-93 ret proto-oncogene Homo sapiens 0-6 8573606-3 1995 MEN 2A mutations involved cysteine residues in the extracellular domain and induced disulfide-linked homodimerization of the Ret protein on the cell surface, leading to activation of its intrinsic tyrosine kinase. Disulfides 84-93 ret proto-oncogene Homo sapiens 125-128