The Rat trk Protooncogene Product Exhibits Properties Characteristic of the Slow Nerve Growth Factor Receptor

• Published in: Proceedings of the National Academy of Sciences - PNAS 1992-03, Vol.89 (6), p.2374-2378
• Main Authors: Meakin, Susan O., Suter, Ueli, Drinkwater, Catherine C., Welcher, Andrew A., Shooter, Eric M.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Animals; Base Sequence; Biological and medical sciences; Cell Line; Cell lines; Cell receptors; Cell structures and functions; Cellular biology; Complementary DNA; COS cells; DNA - genetics; DNA - isolation & purification; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors; Kinetics; Medical research; Messenger RNA; Molecular and cellular biology; Molecular Sequence Data; nerve growth factor; Nerve Growth Factors - metabolism; Nerve Growth Factors - pharmacology; Nervous system; Neurons; neurotrophin; oncogenes; PC12 Cells; pheochromocytoma; Plasmids; Protein Sorting Signals - genetics; protein-tyrosine kinase; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogenes; rat; Rats; Receptor, trkA; Receptors; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Receptors, Nerve Growth Factor; RNA; RNA, Messenger - genetics; Rodents; Transfection
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.89.6.2374

Two distinct nerve growth factor receptor (NGFR) complexes are present on NGF-responsive cell types; these correspond to 100 kDa and 158 kDa for the fast (fNGFR) and the slow (sNGFR) NGFRs, respectively. Previous studies indicate that each complex is derived from a separate gene product and that the sNGFR contains tyrosine kinase activity. The cDNA encoding the fNGFR has previously been cloned. In this report, a rat trk protooncogene cDNA has been isolated from PC12 cells and Trk has been shown to bind NGF, generating a complex of 158 kDa. Characterization of NGF-Trk interactions indicates that Trk and NGF dissociate more slowly than do NGF and the fNGFR. Moreover, NGF-bound Trk is not destroyed by trypsin digestion whereas the NGF-fNGFR complex is sensitive to trypsin digestion. These observations suggest that the trk protooncogene product, expressed in the absence of the fNGFR, binds NGF with properties characteristic of the sNGFR, which was identified as the high-affinity NGFR on primary neurons and PC12 cells.