| http://purl.uniprot.org/citations/16778204 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16778204 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16778204 | http://www.w3.org/2000/01/rdf-schema#comment | "Thyroid cancer is frequently associated with the oncogenic conversion of the RET receptor tyrosine kinase. RET gene rearrangements, which lead to the generation of chimeric RET/papillary thyroid carcinoma (PTC) oncogenes, occur in PTC, whereas RET point mutations occur in familial multiple endocrine neoplasia type 2 (MEN2) and sporadic medullary thyroid carcinomas (MTC). We showed previously that the expression of the receptor-type protein tyrosine phosphatase J (PTPRJ) is suppressed in neoplastically transformed follicular thyroid cells. We now report that PTPRJ coimmunoprecipitates with wild-type RET and with the MEN2A-associated RET(C634R) oncoprotein but not with the RET/PTC1 and RET-MEN2B isoforms. Using mutated forms of PTPRJ and RET-MEN2A, we show that the integrity of the respective catalytic domains is required for the PTPRJ/RET-MEN2A interaction. PTPRJ expression induces dephosphorylation of the RET(C634R) and, probably via an indirect mechanism, RET/PTC1 oncoproteins on two key RET autophosphorylation sites (Tyr1062 and Tyr905). This results in a significant decrease of RET-induced Shc and extracellular signal-regulated kinase 1/2 phosphorylation levels. In line with this finding, adoptive PTPRJ expression reduced the oncogenic activity of RET(C634R) in an in vitro focus formation assay of NIH3T3 cells. As expected from the coimmunoprecipitation results, the RET(M918T) oncoprotein, which is associated to MEN2B and sporadic MTC, was resistant to the dephosphorylating activity of PTPRJ. Taken together, these findings identify RET as a novel substrate of PTPRJ and suggest that PTPRJ expression levels may affect tumor phenotype associated with RET/PTC1 and RET(C634R) mutants. On the other hand, resistance to PTPRJ may be part of the mechanism of RET oncogenic conversion secondary to the M918T mutation."xsd:string |
| http://purl.uniprot.org/citations/16778204 | http://purl.org/dc/terms/identifier | "doi:10.1158/0008-5472.can-06-0228"xsd:string |
| http://purl.uniprot.org/citations/16778204 | http://purl.org/dc/terms/identifier | "doi:10.1158/0008-5472.can-06-0228"xsd:string |
| http://purl.uniprot.org/citations/16778204 | http://purl.uniprot.org/core/author | "Santoro M."xsd:string |
| http://purl.uniprot.org/citations/16778204 | http://purl.uniprot.org/core/author | "Santoro M."xsd:string |
| http://purl.uniprot.org/citations/16778204 | http://purl.uniprot.org/core/author | "Fusco A."xsd:string |
| http://purl.uniprot.org/citations/16778204 | http://purl.uniprot.org/core/author | "Fusco A."xsd:string |
| http://purl.uniprot.org/citations/16778204 | http://purl.uniprot.org/core/author | "Trapasso F."xsd:string |
| http://purl.uniprot.org/citations/16778204 | http://purl.uniprot.org/core/author | "Trapasso F."xsd:string |
| http://purl.uniprot.org/citations/16778204 | http://purl.uniprot.org/core/author | "Melillo R.M."xsd:string |
| http://purl.uniprot.org/citations/16778204 | http://purl.uniprot.org/core/author | "Melillo R.M."xsd:string |
| http://purl.uniprot.org/citations/16778204 | http://purl.uniprot.org/core/author | "Viglietto G."xsd:string |
| http://purl.uniprot.org/citations/16778204 | http://purl.uniprot.org/core/author | "Viglietto G."xsd:string |
| http://purl.uniprot.org/citations/16778204 | http://purl.uniprot.org/core/author | "Carlomagno F."xsd:string |
| http://purl.uniprot.org/citations/16778204 | http://purl.uniprot.org/core/author | "Carlomagno F."xsd:string |
| http://purl.uniprot.org/citations/16778204 | http://purl.uniprot.org/core/author | "Iuliano R."xsd:string |
| http://purl.uniprot.org/citations/16778204 | http://purl.uniprot.org/core/author | "Iuliano R."xsd:string |
| http://purl.uniprot.org/citations/16778204 | http://purl.uniprot.org/core/author | "Iervolino A."xsd:string |
| http://purl.uniprot.org/citations/16778204 | http://purl.uniprot.org/core/author | "Iervolino A."xsd:string |
| http://purl.uniprot.org/citations/16778204 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |
| http://purl.uniprot.org/citations/16778204 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |
| http://purl.uniprot.org/citations/16778204 | http://purl.uniprot.org/core/name | "Cancer Res."xsd:string |
| http://purl.uniprot.org/citations/16778204 | http://purl.uniprot.org/core/name | "Cancer Res."xsd:string |