The rat trk protooncogene product exhibits properties characteristic of the slow nerve growth factor receptor.
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.
Meakin
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Department of Neurobiology, Stanford University School of Medicine, CA 94305-5401.
Suter
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Drinkwater
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Welcher
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Shooter
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EM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D015870:Gene Expression / Q000187:drug effects; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D016716:PC12 Cells; D010957:Plasmids; D021382:Protein Sorting Signals / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D020917:Receptor, trkA; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor; D014162:Transfection
D009414:Nerve Growth Factors; D021382:Protein Sorting Signals; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; D004247:DNA; D011505:Protein-Tyrosine Kinases; D020917:Receptor, trkA