Post-Translational Modification

Dysfunction in Protein Biology, PARK2 (Parkin), Targeting Post-translational Modification, PARK6 (PINK1), PARK8 (LRRK2)

Post-translational modifications such as S-nitrosylation and phosphorylation have been implicated as factors in PD as well as in other neurodegenerative disorders. Nitrosative stress is thought to negatively impact the normal functions of the endoplasmic reticulum, contributing to the accumulation of misfolded proteins (Uehara, 2007; Benhar et al., 2006). Phosphorylated and truncated forms of alpha-synuclein have also been implicated in PD.

Reference: 
Uehara T. Accumulation of misfolded protein through nitrosative stress linked to neurodegenerative disorders. Antioxid Redox Signal. 2007;9(5):597-601.
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Benhar M, Forrester MT, Stamler JS. Nitrosative stress in the ER: a new role for S-nitrosylation in neurodegenerative diseases. ACS Chem Biol. 2006;1(6):355-8.
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Contributions:
LRRK1-LRRK2: safe or toxic twins?
Heterodimerization of Lrrk1-Lrrk2: Implications for LRRK2-associated Parkinson disease.
Elisa Greggio, UNIPD
16 Feb 2010
A paper recently published in Mechanisms of Ageing and Development proposes a functional and genetic association between LRRK2 and its close homologue LRRK1. PD-associated LRRK1 mutations have not ... 
The substrate hunt continues...
Which LRRK2 kinase substrates identified to date are most likely to be true physiological substrates? What limitations/barriers hinder identification of novel substrates?
Holli Kawadler, MJFF
25 Jan 2010
A recent publication from Mark Cookson's group suggests that 4E-BP is likely not a direct substrate for LRRK2 kinase activity, following up on initial studies by Imai et al. (2008). They confirmed ... 
Independent datasets that agree with each other...LRRK2 autophosphorylation in ROC
Which LRRK2 kinase substrates identified to date are most likely to be true physiological substrates? What limitations/barriers hinder identification of novel substrates?
Mark Cookson, NIH
15 Oct 2009
Brief update; the Iwatsubo group in Tokyo has just published a paper in Biochemistry identifying four sites in the ROC domain that overlap with our own analyses: Ser1403, Thr1404, Thr1410 and ... 
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Research Questions:
Which LRRK2 kinase substrates identified to date are most likely to be true physiological substrates? What limitations/barriers hinder identification of novel substrates?
25 Jan 2010
Mutations in the gene coding for the putative kinase LRRK2 represent some of the most prevalent genetic factors yet linked to Parkinson’s disease, but how these alterations lead to PD-related ... 
Responses: 9
What do we know about the function of LRRK2 in cellular processes that may shed light on its role in PD pathogenesis? Is LRRK2 kinase activity key to this regulation or do other features/functions of LRRK2 contribute?
01 Oct 2009
Mutations in the gene coding for the putative kinase LRRK2 represent some of the most prevalent genetic factors yet linked to Parkinson's disease, but how these alterations lead to PD-related ... 
Responses: 3