Novel transcripts reveal a complex structure of the human TRKA gene and imply the presence of multiple protein isoforms.

Background: Tropomyosin-related kinase A (TRKA) is a nerve growth factor (NGF) receptor that belongs to the tyrosine kinase receptor family. It is critical for the correct development of many types of neurons including pain-mediating sensory neurons and also controls proliferation, differentiation a...

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Publicado en:BMC Neuroscience Vol. 16; pp. 1 - 22
Autores principales: Luberg, Kristi, Park, Rahel, Aleksejeva, Elina, Timmusk, Tőnis, Timmusk, Tõnis
Formato: pictorial research tables/charts Journal Article
Publicado: BioMed Central 11/18/2015
Acceso en línea:Ver este registro en EBSCOhost
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      jtl: BMC Neuroscience
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      dt: 11/18/2015
      vid: 16
      pid: 24147
      pub: BioMed Central
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        111079368
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        111079368
        10.1186/s12868-015-0215-x
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        111079368
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        atl: Novel transcripts reveal a complex structure of the human TRKA gene and imply the presence of multiple protein isoforms.
      aug:
        au:
          Luberg, Kristi
          Park, Rahel
          Aleksejeva, Elina
          Timmusk, Tőnis
          Timmusk, Tõnis
        affil: Department of Gene Technology, Tallinn University of Technology, Akadeemia tee 15, 12618 Tallinn, Estonia
      sug:
        subj:
          RNA
          Tissue Banks
          Receptors, Cell Surface
          Gene Expression Profiling
          Rats
          Animal Studies
          Mice
          Proteins
          Human
      ab: Background: Tropomyosin-related kinase A (TRKA) is a nerve growth factor (NGF) receptor that belongs to the tyrosine kinase receptor family. It is critical for the correct development of many types of neurons including pain-mediating sensory neurons and also controls proliferation, differentiation and survival of many neuronal and non-neuronal cells. TRKA (also known as NTRK1) gene is a target of alternative splicing which can result in several different protein isoforms. Presently, three human isoforms (TRKAI, TRKAII and TRKAIII) and two rat isoforms (TRKA L0 and TRKA L1) have been described.Results: We show here that human TRKA gene is overlapped by two genes and spans 67 kb--almost three times the size that has been previously described. Numerous transcription initiation sites from eight different 5' exons and a sophisticated splicing pattern among exons encoding the extracellular part of TRKA receptor indicate that there might be a large variety of alternative protein isoforms. TrkA genes in rat and mouse appear to be considerably shorter, are not overlapped by other genes and display more straightforward splicing patterns. We describe the expression profile of alternatively spliced TRKA transcripts in different tissues of human, rat and mouse, as well as analyze putative endogenous TRKA protein isoforms in human SH-SY5Y and rat PC12 cells. We also characterize a selection of novel putative protein isoforms by portraying their phosphorylation, glycosylation and intracellular localization patterns. Our findings show that an isoform comprising mainly of TRKA kinase domain is capable of entering the nucleus.Conclusions: Results obtained in this study refer to the existence of a multitude of TRKA mRNA and protein isoforms, with some putative proteins possessing very distinct properties.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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