TrkA amino acids controlling specificity for nerve growth factor

Lori O'Connell, Jo Anne Hongo, Leonard G. Presta, Pantelis Tsoulfas

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Neurotrophins are important for the development and maintenance of the vertebrate nervous system, mediating their signal into the cell by specific interaction with tyrosine kinase receptors of the Trk family. The extracellular portion of the Trk receptors has been previously proposed to consist of a cysteine-rich motif, a leucine-rich motif, a second cysteine- rich motif followed by two immunoglobulin-like domains. Earlier studies have shown that a major neurotrophin-binding site in the Trk receptors resides in the second immunoglobulin-like domain. Although the individual amino acids in TrkA involved in binding to nerve growth factor (NGF) and those in TrkC involved in binding to neurotrophin-3 have been mapped in this domain, the Trk amino acids that provide specificity remained unclear. In this study, a minimum set of residues in the human TrkC second immunoglobulin-like domain, which does not bind nerve growth factor (NGF), were substituted with those from human TrkA. The resulting Trk variant recruited binding of NGF equivalent to TrkA, maintained neurotrophin-3 binding equivalent to TrkC, and also bound brain-derived neurotrophin, although with lower affinity compared with TrkB. This implies that the amino acids in the second immunoglobulin- like domain that determine Trk specificity are distinct for each Trk.

Original languageEnglish
Pages (from-to)7870-7877
Number of pages8
JournalJournal of Biological Chemistry
Volume275
Issue number11
DOIs
StatePublished - Mar 17 2000

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Nerve Growth Factor
Immunoglobulins
Nerve Growth Factors
Neurotrophin 3
Amino Acids
Cysteine
Receptor Protein-Tyrosine Kinases
Neurology
Leucine
Cell Communication
Nervous System
Vertebrates
Brain
Binding Sites
Maintenance
Immunoglobulin Domains

ASJC Scopus subject areas

  • Biochemistry

Cite this

TrkA amino acids controlling specificity for nerve growth factor. / O'Connell, Lori; Hongo, Jo Anne; Presta, Leonard G.; Tsoulfas, Pantelis.

In: Journal of Biological Chemistry, Vol. 275, No. 11, 17.03.2000, p. 7870-7877.

Research output: Contribution to journalArticle

O'Connell, Lori ; Hongo, Jo Anne ; Presta, Leonard G. ; Tsoulfas, Pantelis. / TrkA amino acids controlling specificity for nerve growth factor. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 11. pp. 7870-7877.
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