The TrK Receptor Family

Hondermarck, Hubert; Demont, Yohann; Bradshaw, Ralph A.

doi:10.1007/978-3-319-11888-8_17

Cited by 3 publications

(3 citation statements)

References 287 publications

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“…The long and truncated isoforms of the receptor were considered because of the different signalling pathways and functions. TrkB-FL, upon neurotrophin binding, leads to cell differentiation, proliferation and survival; TrkB-T1 is the dominant-negative receptor that inhibits TrkB-FL signalling, and is also known to be expressed in non-neuronal tissue such as astrocytes, bone marrow brain, heart, skeletal muscles, lungs, kidneys, and pancreas (Hondermarck et al, 2015). The TrkB-T1 pathways include regulation of extracellular BDNF concentration, activation of calcium release from intracellular stores and other intracellular signalling pathways through PKC and PLC␥ signalling cascades (Huang and Reichardt, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…However, as the TrkB-FL, TrkB-Shc still retains the binding site for the protein Shc and its expression varies in the same way as TrkB-FL. In addition, the TrkB-Shc receptor isoform is a membrane-bound protein, located exclusively in the brain (Stoilov et al, 2002), while the isoform TrkB-T1 is expressed ubiquitously, but predominantly in the bone marrow brain, heart, skeletal muscles, lungs, kidneys, and pancreas (Hondermarck et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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Distribution of BDNF and TrkB isoforms in growing antler tissues of red deer

Colitti

2017

Annals of Anatomy - Anatomischer Anzeiger

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Distribution of BDNF and TrkB isoforms in growing antler tissues of red deer

Colitti

2017

Annals of Anatomy - Anatomischer Anzeiger

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“…Another subfamily of RTKs with multiple known heterointeractions is the tropomyosin-related kinases (Trks). This subfamily of RTKs is important for the development of the primary and periphery nervous system; the survival, maintenance, and differentiation of neurons; and the transduction of sensory signals. − They primarily bind neurotrophinswhich are NGF, BDNF, neurotrophin 3 (NT-3), and neurotrophin 4/5 (NT-4/5) in mammalsbut can also be activated by a wide range of other factors . Trk overexpression and mutations are associated with a wide variety of cancers, making them an attractive therapeutic target, , as well as a wide range of neurological disorders, including Alzheimer’s, , depression, and schizophrenia …”

Section: Overview Of Known Rtk Cross-subfamily Heterointeractionsmentioning

confidence: 99%

The RTK Interactome: Overview and Perspective on RTK Heterointeractions

Paul

Hristova

2018

Chem. Rev.

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Receptor tyrosine kinases (RTKs) play important roles in cell growth, motility, differentiation, and survival. These single-pass membrane proteins are grouped into subfamilies based on the similarity of their extracellular domains. They are generally thought to be activated by ligand binding, which promotes homodimerization and then autophosphorylation in trans. However, RTK interactions are more complicated, as RTKs can interact in the absence of ligand and heterodimerize within and across subfamilies. Here, we review the known cross-subfamily RTK hetero-interactions and their possible biological implications, as well as the methodologies which have been used to study them. Moreover, we demonstrate how thermodynamic models can be used to study RTKs and to explain many of the complicated biological effects which have been described in the literature. Finally, we discuss the concept of the RTK interactome: a putative, extensive network of interactions between the RTKs. This RTK interactome can produce unique signaling outputs; can amplify, inhibit, and modify signaling; and can allow for signaling backups. The existence of the RTK interactome could provide an explanation for the irreproducibility of experimental data from different studies and for the failure of some RTK inhibitors to produce the desired therapeutic effects. We argue that a deeper knowledge of RTK interactome thermodynamics can lead to a better understanding of fundamental RTK signaling processes in health and disease. We further argue that there is a need for quantitative, thermodynamic studies that probe the strengths of the interactions between RTKs and their ligands and between different RTKs.

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Insight into the Association between Slitrk Protein and Neurodevelopmental and Neuropsychiatric Conditions

Puranik,

Song

2024

Biomolecules

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Slitrk proteins belong the leucine-rich repeat transmembrane family and share structural similarities with the Slits and tropomyosin receptor kinase families, which regulate the development of the nervous system. Slitrks are highly expressed in the developing nervous system of vertebrates, modulating neurite outgrowth and enhancing synaptogenesis; however, the expression and function of Slitrk protein members differ. Slitrk protein variations have been associated with various sensory and neuropsychiatric conditions, including myopia, deafness, obsessive–compulsive disorder, autism spectrum disorders, schizophrenia, attention-deficit/hyperactivity disorder, glioma, and Tourette syndrome; however, the underlying mechanism remains unclear. Therefore, the Slitrk family members’ protein expression, roles in the signaling cascade, functions, and gene mutations need to be comprehensively studied to develop therapeutics against neurodegenerative diseases. This study presents complete and pertinent information demonstrating the relationship between Slitrk family proteins and neuropsychiatric illnesses. This review briefly discusses neurodevelopmental disorders, the leucine-rich repeat family, the Slitrk family, and the association of Slitrk with the neuropathology of representative disorders.

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The TrK Receptor Family

Cited by 3 publications

References 287 publications

Distribution of BDNF and TrkB isoforms in growing antler tissues of red deer

Distribution of BDNF and TrkB isoforms in growing antler tissues of red deer

The RTK Interactome: Overview and Perspective on RTK Heterointeractions

Insight into the Association between Slitrk Protein and Neurodevelopmental and Neuropsychiatric Conditions

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