PXD006045

PXD006045 is an original dataset announced via ProteomeXchange.

Title	Cross-talk between PKA and PKG controls pH-dependent host cell egress of Toxoplasma gondii
Description	Toxoplasma gondii encodes three Protein Kinase A catalytic (PKAc1-3) and one regulatory (PKAr) subunits to integrate cAMP-dependent signals. Here, we show that inactive PKAc1 is maintained at the parasite pellicle by interacting with dually acylated PKAr. Either a conditional knockdown of PKAr or the overexpression of PKAc1 results in a block in parasite division. In contrast, conditional expression of a dominant negative PKAr isoform unable to bind cAMP, triggers premature egress of parasites from infected cells. This untimely egress critically depends on parasite density and host cell acidification. A comparative phosphoproteome analysis reveals that PKA genetic inhibition significantly changed the phosphorylation profile of a putative cGMP-phosphodiesterase, PDE2. Consistently, the phenotype of PKA genetic inhibition is alleviated by chemical inhibition of the cGMP-dependent protein kinase G (PKG). A phosphodiesterase inhibitor is able to circumvent egress repression by PKA or pH neutralisation, indicating that environmental acidification and PKA signalling act as balancing regulators of cGMP degradation to control PKG-mediated egress. Collectively, these results reveal a cross-talk between PKA and PKG pathways to govern egress in T. gondii.
HostingRepository	PRIDE
AnnounceDate	2017-10-12
AnnouncementXML	Submission_2017-11-08_04:32:05.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	James Wright
SpeciesList	scientific name: Toxoplasma gondii; NCBI TaxID: 5811;
ModificationList	phosphorylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2017-03-07 07:51:49	ID requested
1	2017-10-12 03:27:03	announced
⏵ 2	2017-11-08 04:32:06	announced	Updated publication reference for PubMed record(s): 29030485.

Jia Y, Marq JB, Bisio H, Jacot D, Mueller C, Yu L, Choudhary J, Brochet M, Soldati-Favre D, . EMBO J, 36(21):3250-3267(2017) [pubmed]

curator keyword: Biological

submitter keyword: LC-MSMS, IMAC, Phospho, T. gondii

Jyoti Choudhary
contact affiliation	Wellcome Trust Sanger Institute
contact email	jc4@sanger.ac.uk
lab head
James Wright
contact affiliation	Proteomic Mass Spectrometry, Wellcome Trust Sanger Institute
contact email	jw13@sanger.ac.uk
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/2017/10/PXD006045

PRIDE project URI

• PRIDE
  1. PXD006045
     1. Label: PRIDE project
     2. Name: Cross-talk between PKA and PKG controls pH-dependent host cell egress of Toxoplasma gondii