Analysis of the human TrkB gene genomic organization reveals novel TrkB isoforms, unusual gene length, and splicing mechanism

Peter Stoilov, Stefan Stamm, Eero Castren

Research output: Contribution to journalArticlepeer-review

129 Scopus citations

Abstract

We determined the gene structure of the human TrkB gene. The gene is unusually large and spans at least 590 kbp. It contains 24 exons. Using alternative promoters, splicing, and polyadenylation sites, the gene can create at least 100 isoforms, that can encode 10 proteins. RT-PCR and Northern blot analysis reveals that only three major protein isoforms are generated by the gene: The full length receptor, an isoform lacking the tyrosine kinase domain, and a novel isoform lacking the tyrosine kinase domain but containing a Shc binding site. This novel isoform, TrkB-T-Shc is generated by the use of a new alternative exon 19. It is expressed only in brain. TrkB-T-Shc protein is located in the plasma membrane. Coimmunoprecipitation experiments show that TrkB-T-Shc is not phosphorylated by the full length receptor, indicating that it could be a negative regulator of TrkB signaling in the brain.

Original languageEnglish
Pages (from-to)1054-1065
Number of pages12
JournalBiochemical and Biophysical Research Communications
Volume290
Issue number3
DOIs
StatePublished - 2002

Bibliographical note

Funding Information:
This work was supported by grants from the European Union (ERBIO4CT980259) and the Deutsche Forschungsgemeinschaft (Sta3993-1 and SFB473/C8). We are grateful to Joost Verhaagen and Daniela Glockenhammer for helpful discussion and reagents.

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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