PXD036956

PXD036956 is an original dataset announced via ProteomeXchange.

Title	Identification of novel kinases of Tau using fluorescence complementation mass spectrometry (FCMS)
Description	Hyperphosphorylation of the microtubule-associated protein Tau is a major hallmark of Alzheimer’s disease (AD) and other tauopathies. Understanding the protein kinases that phosphorylate Tau is critical for the development of new drugs that target Tau phosphorylation. At present, the repertoire of the Tau kinases remains incomplete, and methods to uncover novel upstream protein kinases are still limited. Here, we apply our newly developed proteomic strategy, fluorescence complementation mass spectrometry (FCMS), to identify novel kinase candidates of Tau. By constructing Tau- and kinase-fluorescent fragment library, we detected 59 Tau-associated kinases, including 23 known kinases of Tau and 36 novel candidate kinases. In the validation phase using in vitro phosphorylation, 17 candidate kinases were successfully expressed and purified, and four candidate kinases, OXSR1, DAPK2, CSK, and ZAP70, displayed the ability to phosphorylate Tau. Furthermore, co-expression of these four kinases along with Tau increased the phosphorylation of Tau in human neuroglioma H4 cells. We demonstrate that FCMS is a powerful proteomic strategy to systematically identify potential kinases that can phosphorylate Tau in cells. Our discovery of new candidate kinases of Tau can present new opportunities for developing AD therapeutic strategies.
HostingRepository	jPOST
AnnounceDate	2022-11-10
AnnouncementXML	Submission_2023-07-13_08:47:54.097.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Der-Shyang Kao
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	S-carboxamidomethyl-L-cysteine; alpha-amino acetylated residue; L-methionine sulfoxide; O-phospho-L-serine; O-phospho-L-threonine; O4'-phospho-L-tyrosine; TMT6plex reporter+balance reagent N-acylated residue; TMT6plex reporter+balance reagent acylated N-terminal
Instrument	instrument; instrument; instrument

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-23 08:00:04	ID requested
1	2022-11-10 11:46:01	announced
⏵ 2	2023-07-13 08:47:54	announced	2023-07-14: Updated PubMed.

Kao DS, Du Y, DeMarco AG, Min S, Hall MC, Rochet JC, Tao WA, Identification of Novel Kinases of Tau Using Fluorescence Complementation Mass Spectrometry (FCMS). Mol Cell Proteomics, 21(12):100441(2022) [pubmed]

submitter keyword: kinases, Tau

W. Andy Tao
lab head
Der-Shyang Kao
contact affiliation	Purdue University
dataset submitter

jPOST dataset URI

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