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The TrK Receptor Family

  • Chapter
Receptor Tyrosine Kinases: Family and Subfamilies

Abstract

The Trk family is composed of three principal members (A, B and C), also termed neurotrophin tyrosine kinase receptors (NTRK1, NTRK2, NTRK3), with several additional splice variants, which in humans are located on three different chromosomes (1, 9, 15). The Trk proteins are receptors for the neurotrophin family of growth factors (NGF, BDNF, NT-3, and NT4/5); they also bind and respond more weakly to the proforms of these neurotrophins. Both the neurotrophins and pro-neurotrophins utilize other receptors (p75NTR, sortilin) that can interact with the Trks and affect their activity. The Trks are predominantly expressed in nervous tissues, where they are essential for the growth, development, and maintenance of select types of both peripheral and central neurons and are involved in neurodegenerative diseases. The Trks are also found in some nonneuronal tissues and in a wide variety of tumors, where they can play an active role in tumor progression and metastasis. The activated Trk receptors primarily bind and signal through Shc, FRS2, and PLCγ, which in turn activate PI3K, the Erks, and the hydrolysis of inositol phospholipids, among other events, leading to the modulation of gene transcription.

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Author information

Authors and Affiliations

  1. School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, 2308, Australia

    Hubert Hondermarck

  2. Centre de Recherche des Cordeliers, INSERM, U1138, 75006, Paris, France

    Yohann Demont

  3. Department of Pharmaceutical Chemistry, University of California, 94158, San Francisco, CA, USA

    Ralph A. Bradshaw

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  1. Hubert Hondermarck
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  2. Yohann Demont
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  3. Ralph A. Bradshaw
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Correspondence to Ralph A. Bradshaw .

Editor information

Editors and Affiliations

  1. School of Medicine and Public Health Department of Human Oncology, University of Wisconsin, Madison, Wisconsin, USA

    Deric L. Wheeler

  2. Department of Biological Regulation, Rehovot, Israel

    Yosef Yarden

Receptor at a glance: TrkA—NTRK1

Receptor at a glance: TrkA—NTRK1

Chromosome location

1q21q22

Gene size (bp)

66,211

Exon numbers

17

mRNA size (5′, ORF, 3′) (bp)

2,663

Amino acid number

Depending on isoform (See Table 17.2)

Molecular mass (kDa)

~140

Posttranslational modifications

Glycosylation, phosphorylation, ubiquitination

Domains

Extracellular, transmembrane, tyrosine kinase

Ligands

NGF, NTF3

Known dimerizing partners

P75NTR, TrkB, TrkC

Pathways activated

MAP kinases, PLCγ, Src, PI3K

Tissues expressed

Broad spectrum of normal/pathological neural and nonneural tissues

Human diseases

Neurodegenerative diseases, cancer

Knockout mouse phenotype

CNS deficit with lack of both nociceptive and superior cervical ganglion neurons

Receptor at a glance: TrkB—NTRK2

Chromosome location

9q22.1

Gene Size (bp)

355,040

Exon numbers

24

mRNA size (5′, ORF, 3′)(bp)

2,663

Amino acid number

Depending on isoform (see Table 17.3)

Molecular mass (kDa)

~140

Posttranslational modifications

Glycosylation, phosphorylation, ubiquitination

Domains

Intracellular tyrosine kinase

Ligands

BDNF, NTF4/5

Known dimerizing partners

P75NTR, TrkA, TrkC

Pathways activated

MAP kinases, PLCγ, Src, PI3K

Tissues expressed

Broad spectrum of normal/pathological neural and nonneural tissues

Human diseases

Neurodegenerative diseases, cancer

Knockout mouse phenotype

CNS deficit with lack of nodose, vestibular, and cochlear neurons; mice display CNS deficits

Receptor at a glance: TrkC—NTRK3

Chromosome location

15q25

Gene size (bp)

397,018

Exon numbers

20

mRNA size (5′, ORF, 3′) (bp)

2,818

Amino acid number

Depending on isoform (See Table 17.4)

Molecular mass (kDa)

~140

Post‐translational modifications

Glycosylation, phosphorylation

Domains

Intracellular tyrosine kinase

Ligands

NTF3

Known dimerizing partners

P75NTR, TrkA, TrkB

Pathways activated

MAP kinases, PLCγ, Src, PI3K

Tissues expressed

CNS, liver, prostate, and breast cancer

Human diseases

Neurodegenerative disease, cancer

Knockout mouse phenotype

CNS deficits with lack of proprioceptive and cochlear neurons; reduction in vestibular neurons

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Hondermarck, H., Demont, Y., Bradshaw, R.A. (2015). The TrK Receptor Family. In: Wheeler, D., Yarden, Y. (eds) Receptor Tyrosine Kinases: Family and Subfamilies. Springer, Cham. https://doi.org/10.1007/978-3-319-11888-8_17

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