High affinity nerve growth factor receptor


Function

High affinity nerve growth factor receptor (TrkA) is a tyrosine kinase receptor. Trk stands for Topomyosin-Related Kinase. TrkA ligand - nerve growth factor activates the receptor by stabilizing homodimer formation which initiates transautophosphorylation[1]. See also Neurotrophin.

Relevance

TrkA has a role in the pathogenesis of psoriasis and its inhibitors are studied in the development of novel therapeutics for the disease[1]. TrkA inhibition may be a novel therapeutic approach to Alzheimer disease[2] and a new method to treat intractable pain[3].

Structural highlights

. An , conserved in all neutrophins, forms the most important binding determinant between TrkA and its ligand - nerve growth factor - which forms the active homodimer of the receptor[4], [5]. .


Glycosylated human TrkA (cyan and green) complex with nerve growth factor (yellow and magenta) (PDB code 2ifg)

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3D structures of high affinity nerve growth factor receptor3D structures of high affinity nerve growth factor receptor

Updated on 16-May-2023

ReferencesReferences

  1. 1.0 1.1 Gill JS, Windebank AJ. Direct activation of the high-affinity nerve growth factor receptor by a non-peptide symmetrical polyanion. Neuroscience. 1998 Dec;87(4):855-60. PMID:9759973
  2. Zhang Q, Descamps O, Hart MJ, Poksay KS, Spilman P, Kane DJ, Gorostiza O, John V, Bredesen DE. Paradoxical effect of TrkA inhibition in Alzheimer's disease models. J Alzheimers Dis. 2014;40(3):605-617. doi: 10.3233/JAD-130017. PMID:24531152 doi:http://dx.doi.org/10.3233/JAD-130017
  3. Hirose M, Kuroda Y, Murata E. NGF/TrkA Signaling as a Therapeutic Target for Pain. Pain Pract. 2016 Feb;16(2):175-82. doi: 10.1111/papr.12342. Epub 2015 Aug 27. PMID:26452158 doi:http://dx.doi.org/10.1111/papr.12342
  4. Wehrman T, He X, Raab B, Dukipatti A, Blau H, Garcia KC. Structural and mechanistic insights into nerve growth factor interactions with the TrkA and p75 receptors. Neuron. 2007 Jan 4;53(1):25-38. PMID:17196528 doi:10.1016/j.neuron.2006.09.034
  5. Wiesmann C, Ultsch MH, Bass SH, de Vos AM. Crystal structure of nerve growth factor in complex with the ligand-binding domain of the TrkA receptor. Nature. 1999 Sep 9;401(6749):184-8. PMID:10490030 doi:10.1038/43705

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