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Exploring Missense Mutations in Tyrosine Kinases Implicated with Neurodegeneration

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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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  1. Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India

    Neha Sami, Vijay Kumar, Asimul Islam, Sher Ali, Faizan Ahmad & Imtaiyaz Hassan

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  1. Neha Sami
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Correspondence to Imtaiyaz Hassan.

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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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