Transphosphorylation of the neurotrophin Trk receptors.
The potential for the activation of one Trk receptor by ligand binding to another Trk receptor was explored by determining if transphosphorylation on tyrosine residues can occur between receptors. For most of these experiments, functional chimeric receptors were used that contained the extracellular domain of the human type 2 tumor necrosis factor receptor and the transmembrane and cytoplasmic domains of rat TrkA, TrkB, or TrkC and that, when activated by the tumor necrosis factor, mediated the nerve growth factor-like biological activities in PC12 cells. Cotransfection experiments in COS-7 cells and fibroblasts showed that despite the presence of different extracellular regions, intermolecular transphosphorylation of homologous cytoplasmic domains occurred between TrkA or TrkB and their cognate chimeras. Heterologous transphosphorylation between TrkB and TrkC kinase domains was also observed when one partner was a chimeric receptor; however, TrkA did not transphosphorylate the TrkB or TrkC kinase domains of chimeric receptors or act as a transphosphorylation substrate for these two receptors. The failure of TrkA to take part in transphosphorylation reactions with TrkB and TrkC was confirmed using the natural receptors. Trk receptor transphosphorylation occurs in the two non-neuronal cell types, but TrkA is excluded from these reactions.
Canossa
M
M
Department of Neurobiology, Stanford University School of Medicine, Stanford, California 94305-5401, USA.
Rovelli
G
G
ShooterEM
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D017931:DNA Primers; D018274:Electroporation; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D016501:Neurites / Q000502:physiology; D016716:PC12 Cells; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000378:metabolism*; D020917:Receptor, trkA; D020813:Receptor, trkB; D020812:Receptor, trkC; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D017931:DNA Primers; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D019000:Phosphotyrosine; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; D020813:Receptor, trkB; D020812:Receptor, trkC