The trk proto-oncogene rescues NGF responsiveness in mutant NGF-nonresponsive PC12 cell lines

David M. Loeb; Johnna Maragos; Dionisio Martin-Zanca; Moses V. Chao; Luis F. Parada; Lloyd A. Greene

doi:10.1016/0092-8674(91)90441-Z

The trk proto-oncogene rescues NGF responsiveness in mutant NGF-nonresponsive PC12 cell lines

David M. Loeb, Johnna Maragos, Dionisio Martin-Zanca, Moses V. Chao, Luis F. Parada, Lloyd A. Greene

Developmental Biology

Research output: Contribution to journal › Article › peer-review

196 Scopus citations

Abstract

The trk tyrosine kinase proto-oncogene product gp140^prototrk binds nerve growth factor (NGF) and is rapidly and selectively activated by this neurotrophic factor. To determine whether gp140^prototrk 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 gp140^prototrk is necessary for functional NGF signal transduction.

Original language	English (US)
Pages (from-to)	961-966
Number of pages	6
Journal	Cell
Volume	66
Issue number	5
DOIs	https://doi.org/10.1016/0092-8674(91)90441-Z
State	Published - Sep 6 1991

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/0092-8674(91)90441-Z

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title = "The trk proto-oncogene rescues NGF responsiveness in mutant NGF-nonresponsive PC12 cell lines",

abstract = "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.",

author = "Loeb, {David M.} and Johnna Maragos and Dionisio Martin-Zanca and Chao, {Moses V.} and Parada, {Luis F.} and Greene, {Lloyd A.}",

note = "Funding Information: Kevin A. Phelan for helpful advice, and Susan Reid for technical assistance. This work was supported in part by grants from the National Institutes of Health (NS 16036 and NS 27680 to L. A. G., NS 21072 and HD 23115 to M. V. C.), by NCI contract NOl-CO-74101 with Advanced Biosciences Laboratory (L. F. P.), and by grants from the American Cancer Society (CD 480) and the HirschlMleill Caulier Trust (to M. V. C.). D. M. L. was supported by MSTP grant GM 07367.",

year = "1991",

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T1 - The trk proto-oncogene rescues NGF responsiveness in mutant NGF-nonresponsive PC12 cell lines

AU - Loeb, David M.

AU - Maragos, Johnna

AU - Martin-Zanca, Dionisio

AU - Chao, Moses V.

AU - Parada, Luis F.

AU - Greene, Lloyd A.

N1 - Funding Information: Kevin A. Phelan for helpful advice, and Susan Reid for technical assistance. This work was supported in part by grants from the National Institutes of Health (NS 16036 and NS 27680 to L. A. G., NS 21072 and HD 23115 to M. V. C.), by NCI contract NOl-CO-74101 with Advanced Biosciences Laboratory (L. F. P.), and by grants from the American Cancer Society (CD 480) and the HirschlMleill Caulier Trust (to M. V. C.). D. M. L. was supported by MSTP grant GM 07367.

PY - 1991/9/6

Y1 - 1991/9/6

N2 - 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.

AB - 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.

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The trk proto-oncogene rescues NGF responsiveness in mutant NGF-nonresponsive PC12 cell lines

Abstract

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