PXD004213

PXD004213 is an original dataset announced via ProteomeXchange.

Title	The innate immunity kinase TAK1 phosphorylates Rab1 on a hotspot for post-translational modifications by host and pathogen
Description	TGF-β Activated Kinase 1 (TAK1) is a critical signaling hub responsible for translating antigen binding signals to immune receptors for the activation of the AP-1 and NF-κB master transcriptional programs. Despite its importance, known substrates of TAK1 are limited to kinases of the MAPK and IKK families and include no direct effectors of biochemical processes. Here, we identify over 200 novel substrates of TAK1 using a chemical genetic kinase strategy. We validate phosphorylation of the dynamic switch II region of GTPase Rab1 at T75 to be regulated by TAK1 in vivo. TAK1 preferentially phosphorylates the inactive (GDP-bound) state of Rab1. Phosphorylation of Rab1 disrupts interaction with GDP Dissociation Inhibitor 1 (GDI1), but not GEF or GAP proteins, and is exclusive to membrane localized Rab1, suggesting phosphorylation may stimulate Rab1 activation and membrane association. We found phosphorylation of Rab1 at T75 to be necessary for normal Rab1 mediated ER to Golgi vesicular transport. Previous studies established that the pathogen Legionella pneumophila is capable of hijacking Rab1 function through post-translational modifications of the switch II region. Here, we present the first evidence that Rab1 is regulated by the host in a similar fashion; and that the innate immunity kinase TAK1 and Legionella effectors compete directly to regulate Rab1 by switch II modifications during infection.
HostingRepository	PRIDE
AnnounceDate	2019-07-15
AnnouncementXML	Submission_2019-07-15_06:50:15.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rebecca Levin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2016-05-24 01:24:22	ID requested
1	2016-07-19 05:45:25	announced
⏵ 2	2019-07-15 06:50:16	announced	Updated publication reference for PubMed record(s): 27482120.

Levin RS, Hertz NT, Burlingame AL, Shokat KM, Mukherjee S, Innate immunity kinase TAK1 phosphorylates Rab1 on a hotspot for posttranslational modifications by host and pathogen. Proc Natl Acad Sci U S A, 113(33):E4776-83(2016) [pubmed]

curator keyword: Biomedical

submitter keyword: kinase, kinase substrates, covalent capture, analog specific kinase

Kevan Shokat
contact affiliation	University of California, San Francisco Howard Hughes Medical Institute
contact email	kevan.shokat@ucsf.edu
lab head
Rebecca Levin
contact affiliation	UCSF
contact email	rebecca.levin@ucsf.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2016/07/PXD004213

PRIDE project URI

• PRIDE
  1. PXD004213
     1. Label: PRIDE project
     2. Name: The innate immunity kinase TAK1 phosphorylates Rab1 on a hotspot for post-translational modifications by host and pathogen