Oncogenic rearrangements of the NTRK1 gene, which encodes the Trk A protein, are frequently detected in thyroid carcinomas. Such rearrangements fuse the NTRK1 tyrosine kinase domain to 5'-end sequences of different genes. TRK-T3 contains 1,412 nucleotides of NTRK1 preceded by 598 nucleotides belonging to TFG (TRK-fused gene), a ubiquitously expressed gene located on chromosome 3. The TRK-T3 protein within the TFG region contains a coiled-coil motif that gives the oncoprotein the capability to form complexes. The cytoplasmic TRK-T3 protein binds to and phosphorylates the Shc and SNT1/FRS2 adaptor proteins, both of which are involved in coupling the receptor tyrosine kinase to the mitogen-activated protein kinase pathway by recruiting Grb2/SOS. SHP-1 also interacts with and down-regulates TRK-T3.