The trk proto-oncogene rescues NGF responsiveness in mutant NGF-nonresponsive PC12 cell lines.
The trk tyrosine kinase proto-oncogene product gp140prototrk binds nerve growth factor (NGF) and is rapidly and selectively activated by this neurotrophic factor. To determine whether gp140prototrk is involved in transducing a functional NGF signal, PC12 cell mutants (PC12nnr) deficient in high affinity NGF binding and unresponsive to NGF were used. Northern analysis revealed that these mutant cells have greatly reduced levels of trk expression. PC12nnr cultures were transiently transfected with expression vectors encoding the full-length rat trk cDNA and assessed for responsiveness to NGF. Expression of exogenous trk rescued the capacity for NGF-promoted neurite outgrowth, cellular hypertrophy, and serum-free survival by these cells. These results indicate that gp140prototrk is necessary for functional NGF signal transduction.
Loeb
D M
DM
Department of Pathology, College of Physicians and Surgeons Columbia University, New York, New York 10032.
Maragos
J
J
Martin-Zanca
D
D
Chao
M V
MV
Parada
L F
LF
Greene
L A
LA
D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000473:pathology; D000818:Animals; D015152:Blotting, Northern; D002227:Carbazoles / Q000494:pharmacology; D002454:Cell Differentiation; D002455:Cell Division; D002470:Cell Survival; D015870:Gene Expression; D066298:In Vitro Techniques; D026121:Indole Alkaloids; D009414:Nerve Growth Factors / Q000502:physiology*; D010673:Pheochromocytoma / Q000503:physiopathology; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D020917:Receptor, trkA; D011956:Receptors, Cell Surface / Q000502:physiology*; D017475:Receptors, Nerve Growth Factor; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured
D002227:Carbazoles; D026121:Indole Alkaloids; D009414:Nerve Growth Factors; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; C049985:staurosporine aglycone; D011505:Protein-Tyrosine Kinases; D020917:Receptor, trkA