The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

RET/PTC-induced dedifferentiation of thyroid cells is mediated through Y1062 signaling through SHC-RAS-MAP kinase.

Constitutive activation of the RET proto-oncogene in papillary thyroid carcinomas results from rearrangements linking the promoter(s) and N-terminal domains of unrelated genes to the C-terminus of RET tyrosine kinase (RET/PTC). RET/PTC expression has been demonstrated to inhibit transcription of thyroid-specific genes. To study the signal transduction pathways responsible for this, we generated PCCL3 thyroid cells with doxycycline-inducible expression of RET/PTC3, RET/PTC3(Y541F), or PTC2/PDZ. Acute expression of RET/PTC(Y541F) appropriately interacted with Shc, an intermediate in the activation of the Ras pathway, but failed to activate PLCgamma. By contrast, PTC2/PDZ failed to bind Shc, but interacted normally with PLCgamma. Acute expression of RET/PTC3 or RET/PTC3(Y541F), but not PTC2/PDZ, inhibited TSH-induced Tg and NIS expression, suggesting that activation of Shc-Ras, but not PLCgamma, is required for RET/PTC-induced dedifferentiation. Accordingly, acute expression of H-Ras(V12) or of a constitutively active MEK1 also blocked TSH-induced expression of Tg and NIS. Moreover, MEK inhibitors restored Tg and NIS levels. In conclusion, activation of the Ras/Raf/MEK/MAPK pathway through Shc mediates RET/PTC-induced thyroid cell dedifferentiation. This suggests that inhibition of this pathway may promote redifferentiation in poorly differentiated thyroid carcinomas with constitutive activation of either Ras or RET/PTC.[1]


WikiGenes - Universities