The availability of genome sequence information and a large number of protein structures has allowed the cataloging of genes into various families, based on their function and predicted biochemical activity. Intriguingly, a number of proteins harbor changes in the amino acid sequence at residues, that from structural elucidation, are critical for catalytic activity. Such proteins have been categorized as ‘pseudoenzymes’. Here, we review the role of the pseudokinase (or kinase-homology) domain in receptor guanylyl cyclases. These are multidomain single-pass, transmembrane proteins harboring an extracellular ligand-binding domain, and an intracellular domain composed of a kinase-homology domain that regulates the activity of the associated guanylyl cyclase domain. Mutations that lie in the kinase-homology domain of these receptors are associated with human disease, and either abolish or enhance cGMP production by these receptors to alter downstream signaling events. This raises the interesting possibility that one could identify molecules that bind to the pseudokinase domain and regulate the activities of these receptors, in order to alleviate symptoms in patients harboring these mutations.
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Dysfunctional cytoskeleton and neurodegeneration: novel pathways in Parkinson's disease? This image represents the degeneration of the neuronal tree during the aging process. In this issue Civiero et al. discuss the consequence of impaired cytoskeletal dynamics on neurite morphology and neuronal physiology in Parkinson's disease. For further details see pages 1653–1663.
Review Article|
November 12 2018
The regulatory role of the kinase-homology domain in receptor guanylyl cyclases: nothing ‘pseudo’ about it!
Vishwas Mishra;
Vishwas Mishra
1Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bengaluru, India
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Ridhima Goel;
Ridhima Goel
1Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bengaluru, India
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Sandhya S. Visweswariah
1Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bengaluru, India
Correspondence: Sandhya S. Visweswariah (sandhya@iisc.ac.in)
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Publisher: Portland Press Ltd
Received:
September 15 2018
Revision Received:
October 08 2018
Accepted:
October 11 2018
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Biochem Soc Trans (2018) 46 (6): 1729–1742.
Article history
Received:
September 15 2018
Revision Received:
October 08 2018
Accepted:
October 11 2018
Citation
Vishwas Mishra, Ridhima Goel, Sandhya S. Visweswariah; The regulatory role of the kinase-homology domain in receptor guanylyl cyclases: nothing ‘pseudo’ about it!. Biochem Soc Trans 17 December 2018; 46 (6): 1729–1742. doi: https://doi.org/10.1042/BST20180472
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