An immunoglobulin-like domain determines the specificity of neurotrophin receptors

R. Urfer, P. Tsoulfas, L. O'Connell, D. L. Shelton, L. F. Parada, L. G. Presta

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

The neurotrophins influence survival and maintenance of vertebrate neurons in the embryonic, early postnatal and post-developmental stages of the nervous system. Binding of neurotrophins to receptors encoded by the gene family trk initiates signal transduction into the cell, trkA interacts preferably with nerve growth factor (NGF), trkB with brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5) and trkC with neurotrophin-3 (NT-3). By constructing 17 different chimeras and domain deletions of the human trk receptors and analyzing their binding affinities to the neurotrophins we have shown that an immunoglobulin-like domain located adjacent to the transmembrane domain is the structural element that determines the interaction of neurotrophins with their receptors. Chimeras of trkC where this domain was exchanged for the homologous sequences from trkB or trkA gained high affinity binding to BDNF or NGF respectively, while deletion of this domain in trkC or trkA abolished binding to NT-3 or NGF respectively. This domain alone retained affinities to neurotrophins similar to the full-length receptors and when expressed on NIH 3T3 cells in fusion with the kinase domain showed neurotrophin-dependent activation.

Original languageEnglish (US)
Pages (from-to)2795-2805
Number of pages11
JournalEMBO Journal
Volume14
Issue number12
StatePublished - 1995

Fingerprint

Nerve Growth Factor Receptors
Nerve Growth Factors
Immunoglobulins
Nerve Growth Factor
Neurotrophin 3
Brain-Derived Neurotrophic Factor
NIH 3T3 Cells
Cell Fusion
Signal transduction
Sequence Homology
Nervous System
Neurology
Vertebrates
Signal Transduction
Phosphotransferases
Neurons
Maintenance
Immunoglobulin Domains
Fusion reactions
Genes

Keywords

  • Binding domain
  • Kinase receptor
  • Neutrophios
  • Trk
  • Tyrosine

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

Cite this

Urfer, R., Tsoulfas, P., O'Connell, L., Shelton, D. L., Parada, L. F., & Presta, L. G. (1995). An immunoglobulin-like domain determines the specificity of neurotrophin receptors. EMBO Journal, 14(12), 2795-2805.

An immunoglobulin-like domain determines the specificity of neurotrophin receptors. / Urfer, R.; Tsoulfas, P.; O'Connell, L.; Shelton, D. L.; Parada, L. F.; Presta, L. G.

In: EMBO Journal, Vol. 14, No. 12, 1995, p. 2795-2805.

Research output: Contribution to journalArticle

Urfer, R, Tsoulfas, P, O'Connell, L, Shelton, DL, Parada, LF & Presta, LG 1995, 'An immunoglobulin-like domain determines the specificity of neurotrophin receptors', EMBO Journal, vol. 14, no. 12, pp. 2795-2805.
Urfer R, Tsoulfas P, O'Connell L, Shelton DL, Parada LF, Presta LG. An immunoglobulin-like domain determines the specificity of neurotrophin receptors. EMBO Journal. 1995;14(12):2795-2805.
Urfer, R. ; Tsoulfas, P. ; O'Connell, L. ; Shelton, D. L. ; Parada, L. F. ; Presta, L. G. / An immunoglobulin-like domain determines the specificity of neurotrophin receptors. In: EMBO Journal. 1995 ; Vol. 14, No. 12. pp. 2795-2805.
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