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PXD014794 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePPM1H phosphatase counteracts LRRK2 signaling by selectively dephosphorylating Rab proteins
DescriptionMutations that activate LRRK2 protein kinase cause Parkinson’s disease. LRRK2 phosphorylates a subset of Rab GTPases within their Switch-II motif controlling interaction with effectors. An siRNA screen of all protein phosphatases revealed that a poorly studied protein phosphatase, PPM1H, counteracts LRRK2 signaling by specifically dephosphorylating Rab proteins. PPM1H knock out increased endogenous Rab phosphorylation and inhibited Rab dephosphorylation. Overexpression of PPM1H suppressed LRRK2-mediated Rab phosphorylation. PPM1H also efficiently and directly dephosphorylated Rab8A in biochemical studies. A “substrate-trapping” PPM1H mutant (Asp288Ala) binds with high affinity to endogenous, LRRK2-phosphorylated Rab proteins, thereby blocking dephosphorylation seen upon addition of LRRK2 inhibitors. PPM1H is localized to the Golgi and its knockdown suppresses primary cilia formation, similar to pathogenic LRRK2. Thus, PPM1H acts as a key modulator of LRRK2 signaling by controlling dephosphorylation of Rab proteins. PPM1H activity enhancers could offer a new therapeutic approach to prevent or treat Parkinson’s disease
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterRaja Sekhar Nirujogi
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue; phosphorylated residue; iodoacetamide derivatized residue; deamidated residue
InstrumentOrbitrap Fusion Lumos; Q Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-07-29 01:59:27ID requested
12019-11-06 01:54:56announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: LRRK2, Phosphatase, Parkinson's disease, RAB10
Contact List
Prof. Dario R. Alessi
contact affiliationMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, United Kingdom DD1 5EH, UK
contact emaild.r.alessi@dundee.ac.uk
lab head
Raja Sekhar Nirujogi
contact affiliationMRC Protein Phosphorylation Unit, university of Dundee
contact emailrnirujogi@dundee.ac.uk
dataset submitter
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Dataset FTP location
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