Identification of bona-fide LRRK2 kinase substrates

doi:10.1002/mds.26647

Editorial

. 2016 Aug;31(8):1140-1.

doi: 10.1002/mds.26647. Epub 2016 Apr 29.

Identification of bona-fide LRRK2 kinase substrates

Andrew B West¹, Mark R Cookson²

Affiliations

¹ Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
² Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.

PMID: 27126091
PMCID: PMC4981516
DOI: 10.1002/mds.26647

Editorial

Identification of bona-fide LRRK2 kinase substrates

Andrew B West et al. Mov Disord. 2016 Aug.

. 2016 Aug;31(8):1140-1.

doi: 10.1002/mds.26647. Epub 2016 Apr 29.

Authors

Andrew B West¹, Mark R Cookson²

Affiliations

¹ Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
² Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.

PMID: 27126091
PMCID: PMC4981516
DOI: 10.1002/mds.26647

No abstract available

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Figures

**Figure 1**
A) Threonine or serine residues in Rab receptacles that depend on LRRK2 kinase activity for their phosphorylated state in cells. B) Rabs with serine in switch II residues may not serve as efficient LRRK2 kinase substrates for LRRK2 *in vitro* but are regulated by LRRK2 in cells. Rabs with threonine residues in switch II may serve as direct LRRK2 kinase substrates both *in vitro* and in cells. Blue arrows indicate relative strength of LRRK2-mediate phosphorylation of the switch II receptacles.

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Comment on

Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases.
Steger M, Tonelli F, Ito G, Davies P, Trost M, Vetter M, Wachter S, Lorentzen E, Duddy G, Wilson S, Baptista MA, Fiske BK, Fell MJ, Morrow JA, Reith AD, Alessi DR, Mann M. Steger M, et al. Elife. 2016 Jan 29;5:e12813. doi: 10.7554/eLife.12813. Elife. 2016. PMID: 26824392 Free PMC article.

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References

1. West AB, Moore DJ, Biskup S, et al. Parkinson’s disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(46):16842–16847. - PMC - PubMed
1. Steger M, Tonelli F, Ito G, et al. Phosphoproteomics reveals that Parkinson’s disease kinase LRRK2 regulates a subset of Rab GTPases. Elife. 2016;5 - PMC - PubMed
1. Reynolds A, Doggett EA, Riddle SM, Lebakken CS, Nichols RJ. LRRK2 kinase activity and biology are not uniformly predicted by its autophosphorylation and cellular phosphorylation site status. Front Mol Neurosci. 2014;7:54. - PMC - PubMed
1. Sheng Z, Zhang S, Bustos D, et al. Ser1292 autophosphorylation is an indicator of LRRK2 kinase activity and contributes to the cellular effects of PD mutations. Sci Transl Med. 2012;4(164):164ra161. - PubMed
1. Liu Z, Mobley JA, DeLucas LJ, Kahn RA, West AB. LRRK2 autophosphorylation enhances its GTPase activity. FASEB J. 2016;30(1):336–347. - PMC - PubMed

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[1] West AB, Moore DJ, Biskup S, et al. Parkinson’s disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(46):16842–16847. - PMC - PubMed

[2] West AB, Moore DJ, Biskup S, et al. Parkinson’s disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(46):16842–16847. - PMC - PubMed

[3] Steger M, Tonelli F, Ito G, et al. Phosphoproteomics reveals that Parkinson’s disease kinase LRRK2 regulates a subset of Rab GTPases. Elife. 2016;5 - PMC - PubMed

[4] Steger M, Tonelli F, Ito G, et al. Phosphoproteomics reveals that Parkinson’s disease kinase LRRK2 regulates a subset of Rab GTPases. Elife. 2016;5 - PMC - PubMed

[5] Reynolds A, Doggett EA, Riddle SM, Lebakken CS, Nichols RJ. LRRK2 kinase activity and biology are not uniformly predicted by its autophosphorylation and cellular phosphorylation site status. Front Mol Neurosci. 2014;7:54. - PMC - PubMed

[6] Reynolds A, Doggett EA, Riddle SM, Lebakken CS, Nichols RJ. LRRK2 kinase activity and biology are not uniformly predicted by its autophosphorylation and cellular phosphorylation site status. Front Mol Neurosci. 2014;7:54. - PMC - PubMed

[7] Sheng Z, Zhang S, Bustos D, et al. Ser1292 autophosphorylation is an indicator of LRRK2 kinase activity and contributes to the cellular effects of PD mutations. Sci Transl Med. 2012;4(164):164ra161. - PubMed

[8] Sheng Z, Zhang S, Bustos D, et al. Ser1292 autophosphorylation is an indicator of LRRK2 kinase activity and contributes to the cellular effects of PD mutations. Sci Transl Med. 2012;4(164):164ra161. - PubMed

[9] Liu Z, Mobley JA, DeLucas LJ, Kahn RA, West AB. LRRK2 autophosphorylation enhances its GTPase activity. FASEB J. 2016;30(1):336–347. - PMC - PubMed

[10] Liu Z, Mobley JA, DeLucas LJ, Kahn RA, West AB. LRRK2 autophosphorylation enhances its GTPase activity. FASEB J. 2016;30(1):336–347. - PMC - PubMed

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Identification of bona-fide LRRK2 kinase substrates

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Identification of bona-fide LRRK2 kinase substrates

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