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| Trk family | |
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| Name | Trk family |
Trk family The Trk family comprises a group of receptor tyrosine kinases that mediate neurotrophic signaling and influence neuronal survival, differentiation, and synaptic plasticity. Prominent in vertebrate neurobiology, members of the Trk family interact with neurotrophins and engage pathways studied in contexts such as Nobel Prize in Physiology or Medicine, Cold Spring Harbor Laboratory, Max Planck Institute for Brain Research, Howard Hughes Medical Institute, and Salk Institute for Biological Studies.
The Trk family was discovered through research linking neurotrophic factors to receptor activity in studies by teams at Columbia University, Harvard Medical School, University of California, San Diego, University of Cambridge, and University College London. Early work connected Trk receptors to ligands characterized at National Institutes of Health, Wellcome Trust Sanger Institute, Institute of Cancer Research, Stanford University School of Medicine, and Yale School of Medicine. Subsequent characterization involved collaborations with laboratories at Massachusetts Institute of Technology, Johns Hopkins University, University of Pennsylvania, Cold Spring Harbor Laboratory, and Rockefeller University.
Trk receptors are single-pass transmembrane proteins with extracellular ligand-binding domains, a transmembrane helix, and an intracellular tyrosine kinase domain; structural studies were performed at European Molecular Biology Laboratory, Brookhaven National Laboratory, Lawrence Berkeley National Laboratory, Diamond Light Source, and Argonne National Laboratory. Major vertebrate members include three canonical paralogs heavily studied at National Institute of Neurological Disorders and Stroke, Institut Pasteur, Karolinska Institutet, University of Oxford, and MRC Laboratory of Molecular Biology. High-resolution analyses involved groups from Protein Data Bank, EMBL-EBI, Riken, University of Tokyo, and Max Planck Institute for Biophysical Chemistry. Isoforms, splice variants, and post-translationally modified forms were cataloged by teams at European Bioinformatics Institute, Broad Institute, Wellcome Sanger Institute, Cold Spring Harbor Laboratory, and Swiss Institute of Bioinformatics.
Ligand binding triggers receptor dimerization and autophosphorylation, recruiting adaptor proteins and kinases that engage cascades characterized in experiments at National Institutes of Health, European Molecular Biology Laboratory, Howard Hughes Medical Institute, Yale School of Medicine, and Harvard Medical School. Downstream effectors include pathways elucidated by researchers at Max Planck Institute for Neurobiology, University of California, San Francisco, Massachusetts General Hospital, Salk Institute for Biological Studies, and Cold Spring Harbor Laboratory. Signal transduction intersects with molecules studied at Weizmann Institute of Science, University of Melbourne, Monash University, University of Toronto, and McGill University. Cross-talk with receptors and channels was mapped by teams at Stanford University, Columbia University, Imperial College London, University of Washington, and UCLA.
Trk receptors regulate processes in nervous system development, synaptogenesis, and plasticity documented in work at University of California, Berkeley, Princeton University, Duke University, University of Chicago, and University of Texas Southwestern Medical Center. Roles in sensory neuron function, motor neuron maintenance, and central nervous system circuits were investigated by groups at Karolinska Institutet, University of Copenhagen, Max Planck Institute for Brain Research, University of Edinburgh, and University of Melbourne. Contributions to behavior, learning, and memory were reported from studies at University of Cambridge, Columbia University, Yale University, MIT, and Harvard University.
Dysregulation of Trk signaling has been implicated in neurodegenerative disorders, developmental neuropathies, and psychiatric conditions explored at National Institute of Neurological Disorders and Stroke, Alzheimer's Association, Parkinson's Foundation, Multiple Sclerosis Society, and Autism Speaks. Oncogenic fusions and mutations involving Trk family members were identified in tumor profiling consortia at The Cancer Genome Atlas, International Cancer Genome Consortium, Memorial Sloan Kettering Cancer Center, MD Anderson Cancer Center, and Dana-Farber Cancer Institute. Therapeutic targeting, including small molecules and biologics, is being developed in programs at Roche, Novartis, Pfizer, GlaxoSmithKline, and AstraZeneca and tested in clinical centers such as Mayo Clinic, Cleveland Clinic, and Johns Hopkins Hospital.
Experimental approaches to study Trk receptors include structural biology, biochemistry, genetics, and in vivo models implemented at EMBL, Sanger Institute, Broad Institute, Allen Institute for Brain Science, and Jackson Laboratory. Animal models such as mouse, rat, zebrafish, and Drosophila systems were developed and characterized by laboratories at The Jackson Laboratory, Zebrafish International Resource Center, Max Planck Institute, University of California, San Diego, and Harvard Medical School. Tools include conditional alleles, viral vectors, and optogenetic or chemogenetic strategies produced by groups at Cold Spring Harbor Laboratory, Stanford Neurosciences Institute, MIT McGovern Institute, Howard Hughes Medical Institute, and Salk Institute.
Comparative genomics and phylogenetics of Trk family members were advanced by consortia and institutions including Ensembl, NCBI, UCSC Genome Browser, Wellcome Sanger Institute, and European Bioinformatics Institute. Evolutionary studies across vertebrates and invertebrates involved collaborations with University of Hawaii, Australian National University, University of Cape Town, University of São Paulo, and Peking University. Functional conservation and divergence have been assessed by research teams at Max Planck Institute for Evolutionary Anthropology, Smithsonian Institution, Natural History Museum, London, American Museum of Natural History, and Royal Society.
Category:Receptor tyrosine kinases