Abstract
Protein kinases are one of the largest families of evolutionarily related proteins and the third most common protein class of human genome. All the protein kinases share the same structural organization. They are made up of an extracellular domain, transmembrane domain and an intra cellular kinase domain. Missense mutations in these kinases have been studied extensively and correlated with various neurological disorders. Individual mutations in the kinase domain affect the functions of protein. The enhanced or reduced expression of protein leads to hyperactivation or inactivation of the signalling pathways, resulting in neurodegeneration. Here, we present extensive analyses of missense mutations in the tyrosine kinase focussing on the neurodegenerative diseases encompassing structure function relationship. This is envisaged to enhance our understanding about the neurodegeneration and possible therapeutic measures.
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Abbreviations
- AchR:
-
Acetylcholine receptors
- AIS:
-
Auto-inhibitory sequence
- ALCL:
-
Anaplastic large-cell lymphoma
- ALK:
-
Anaplastic lymphoma receptor tyrosine kinase
- BAD:
-
Bcl-2 associated death promoter
- CDKL5:
-
Cyclin-dependent kinase-like 5
- CIPA:
-
Congenital insensitivity to pain with anhidrosis
- DFG:
-
Asp-Phe-Gly motif
- EGFR:
-
Epidermal growth factor receptor family
- ErbB3:
-
Erythroblastic leukaemia viral oncogene homologue 3
- HER3:
-
Heregulin 3
- HRD:
-
His-Arg-Asp motif
- HSS:
-
Hallervorden-Spatz syndrome
- KA-1:
-
Kinase-associated domain
- LCCS2:
-
Lethal congenital contractual syndrome type 2
- LDLa:
-
Low-density lipoprotein receptor class A
- LRP4:
-
Low-density lipoprotein receptor-related protein 4
- LTK:
-
Leukocyte tyrosine kinase
- MAM:
-
Met-Ala-Met segment
- MuSK:
-
Muscle-specific receptor tyrosine kinase
- NBIA:
-
Neurodegeneration with brain iron accumulation
- NBL:
-
Neuroblastoma
- NPM:
-
Nucleophosmin
- NTRK1:
-
Neurotrophic tyrosine kinase receptor 1
- PANK2:
-
Pantothenate kinase 2
- PINK1:
-
PTEN-induced putative kinase 1
- PKAN:
-
PANK-associated neurodegeneration
- PRKCG:
-
Protein kinase C-γ
- RTKs:
-
Receptor tyrosine kinases
- TKs:
-
Non-receptor tyrosine kinases
- TRPM7:
-
Transient receptor potential melastatin 7
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Acknowledgments
NS sincerely thanks University Grants Commission for awarding Maulana Azad National Fellowship (MANF-JRF). VK thanks Department of Science and Technology for the award of DST-Fast track Fellowship (SB/YS/LS-161/2014). FA and MIH gratefully acknowledge the final support from the Department of Science and Technology, Ministry of Science and Technology (EMR/2015/002372), India. SA is grateful to Department of Science and Technology (DST), Government of India for the award of J. C. Bose National Fellowship. FIST support of DST is highly acknowledged (SR/FST/LSI-541/2012).
Author Contributions
VK conceived, designed and supervised the review. NS and VK wrote the manuscript. VK, AI, SA, FA and MIH analysed the contents and revised the paper. All authors approved the manuscript for publication.
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Sami, N., Kumar, V., Islam, A. et al. Exploring Missense Mutations in Tyrosine Kinases Implicated with Neurodegeneration. Mol Neurobiol 54, 5085–5106 (2017). https://doi.org/10.1007/s12035-016-0046-5
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DOI: https://doi.org/10.1007/s12035-016-0046-5