Characterization of a multicomponent receptor for GDNF

J. J.S. Treanor; L. Goodman; F. De Sauvage; D. M. Stone; K. T. Poulsen; C. D. Beck; C. Gray; M. P. Armanini; R. A. Pollock; F. Hefti; H. S. Phillips; A. Goddard; M. W. Moore; A. Buj-Bello; A. M. Davies; N. Asai; M. Takahashi; R. Vandien; C. E. Henderson; A. Rosenthal

doi:10.1038/382080a0

Characterization of a multicomponent receptor for GDNF

J. J.S. Treanor, L. Goodman, F. De Sauvage, D. M. Stone, K. T. Poulsen, C. D. Beck, C. Gray, M. P. Armanini, R. A. Pollock, F. Hefti, H. S. Phillips, A. Goddard, M. W. Moore, A. Buj-Bello, A. M. Davies, N. Asai, M. Takahashi, R. Vandien, C. E. Henderson, A. Rosenthal

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Abstract

GLIAL-CELL-LINE-DERIVED neurotrophic factor (GDNF) is a potent survival factor for central and peripheral neurons, and is essential for the development of kidneys and the enteric nervous system. Despite the potential clinical and physiological importance of GDNF, its mechanism of action is unknown. Here we show that physiological responses to GDNF require the presence of a novel glycosyl-phosphatidylinositol (GPI)-linked protein (designated GDNFR-α) that is expressed on GDNF-responsive ceils and binds GDNF with a high affinity. We further demonstrate that GDNF promotes the formation of a physical complex between GDNFR-α and the orphan tyrosine kinase receptor Ret, thereby inducing its tyrosine phosphorylation. These findings support the hypothesis that GDNF uses a multi-subunit receptor system in which GDNFR-α and Ret function as the ligand-binding and signalling components, respectively.

Original language	English
Pages (from-to)	80-83
Number of pages	4
Journal	Nature
Volume	382
Issue number	6586
DOIs	https://doi.org/10.1038/382080a0
Publication status	Published - 1996
Externally published	Yes

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Treanor, J. J. S., Goodman, L., De Sauvage, F., Stone, D. M., Poulsen, K. T., Beck, C. D., Gray, C., Armanini, M. P., Pollock, R. A., Hefti, F., Phillips, H. S., Goddard, A., Moore, M. W., Buj-Bello, A., Davies, A. M., Asai, N., Takahashi, M., Vandien, R., Henderson, C. E., & Rosenthal, A. (1996). Characterization of a multicomponent receptor for GDNF. Nature, 382(6586), 80-83. https://doi.org/10.1038/382080a0

@article{7218f3f54ce842459907f4ee3879c99a,

title = "Characterization of a multicomponent receptor for GDNF",

abstract = "GLIAL-CELL-LINE-DERIVED neurotrophic factor (GDNF) is a potent survival factor for central and peripheral neurons, and is essential for the development of kidneys and the enteric nervous system. Despite the potential clinical and physiological importance of GDNF, its mechanism of action is unknown. Here we show that physiological responses to GDNF require the presence of a novel glycosyl-phosphatidylinositol (GPI)-linked protein (designated GDNFR-α) that is expressed on GDNF-responsive ceils and binds GDNF with a high affinity. We further demonstrate that GDNF promotes the formation of a physical complex between GDNFR-α and the orphan tyrosine kinase receptor Ret, thereby inducing its tyrosine phosphorylation. These findings support the hypothesis that GDNF uses a multi-subunit receptor system in which GDNFR-α and Ret function as the ligand-binding and signalling components, respectively.",

author = "Treanor, {J. J.S.} and L. Goodman and {De Sauvage}, F. and Stone, {D. M.} and Poulsen, {K. T.} and Beck, {C. D.} and C. Gray and Armanini, {M. P.} and Pollock, {R. A.} and F. Hefti and Phillips, {H. S.} and A. Goddard and Moore, {M. W.} and A. Buj-Bello and Davies, {A. M.} and N. Asai and M. Takahashi and R. Vandien and Henderson, {C. E.} and A. Rosenthal",

year = "1996",

doi = "10.1038/382080a0",

language = "English",

volume = "382",

pages = "80--83",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

number = "6586",

}

Treanor, JJS, Goodman, L, De Sauvage, F, Stone, DM, Poulsen, KT, Beck, CD, Gray, C, Armanini, MP, Pollock, RA, Hefti, F, Phillips, HS, Goddard, A, Moore, MW, Buj-Bello, A, Davies, AM, Asai, N , Takahashi, M, Vandien, R, Henderson, CE & Rosenthal, A 1996, 'Characterization of a multicomponent receptor for GDNF', Nature, vol. 382, no. 6586, pp. 80-83. https://doi.org/10.1038/382080a0

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T1 - Characterization of a multicomponent receptor for GDNF

AU - Treanor, J. J.S.

AU - Goodman, L.

AU - De Sauvage, F.

AU - Stone, D. M.

AU - Poulsen, K. T.

AU - Beck, C. D.

AU - Gray, C.

AU - Armanini, M. P.

AU - Pollock, R. A.

AU - Hefti, F.

AU - Phillips, H. S.

AU - Goddard, A.

AU - Moore, M. W.

AU - Buj-Bello, A.

AU - Davies, A. M.

AU - Asai, N.

AU - Takahashi, M.

AU - Vandien, R.

AU - Henderson, C. E.

AU - Rosenthal, A.

PY - 1996

Y1 - 1996

N2 - GLIAL-CELL-LINE-DERIVED neurotrophic factor (GDNF) is a potent survival factor for central and peripheral neurons, and is essential for the development of kidneys and the enteric nervous system. Despite the potential clinical and physiological importance of GDNF, its mechanism of action is unknown. Here we show that physiological responses to GDNF require the presence of a novel glycosyl-phosphatidylinositol (GPI)-linked protein (designated GDNFR-α) that is expressed on GDNF-responsive ceils and binds GDNF with a high affinity. We further demonstrate that GDNF promotes the formation of a physical complex between GDNFR-α and the orphan tyrosine kinase receptor Ret, thereby inducing its tyrosine phosphorylation. These findings support the hypothesis that GDNF uses a multi-subunit receptor system in which GDNFR-α and Ret function as the ligand-binding and signalling components, respectively.

AB - GLIAL-CELL-LINE-DERIVED neurotrophic factor (GDNF) is a potent survival factor for central and peripheral neurons, and is essential for the development of kidneys and the enteric nervous system. Despite the potential clinical and physiological importance of GDNF, its mechanism of action is unknown. Here we show that physiological responses to GDNF require the presence of a novel glycosyl-phosphatidylinositol (GPI)-linked protein (designated GDNFR-α) that is expressed on GDNF-responsive ceils and binds GDNF with a high affinity. We further demonstrate that GDNF promotes the formation of a physical complex between GDNFR-α and the orphan tyrosine kinase receptor Ret, thereby inducing its tyrosine phosphorylation. These findings support the hypothesis that GDNF uses a multi-subunit receptor system in which GDNFR-α and Ret function as the ligand-binding and signalling components, respectively.

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JF - Nature

IS - 6586

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Characterization of a multicomponent receptor for GDNF

Abstract

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