PXD001340

PXD001340 is an original dataset announced via ProteomeXchange.

Title	PIP4kγ is a substrate for mTORC1
Description	Phosphatidylinositol-5-phosphate 4-kinases (PIP4ks) are a family of lipid kinases that specifically use PI-5-P as a substrate to synthesize PI-4,5-P2. Suppression of PIP4k function in Drosophila results in smaller cells and reduced target of rapamycin complex 1 (TORC1) signaling. We showed that the γ isoform of PIP4k stimulated signaling through mammalian TORC1 (mTORC1). Knockdown of PIP4kγ reduced cell mass in cells in which mTORC1 is constitutively activated by Tsc2 deficiency. In Tsc2 null cells mTORC1 activation was partially independent of amino acids or glucose and glutamine. PIP4kγ knockdown inhibited the nutrient-independent activation of mTORC1 in Tsc2 knockdown cells and reduced basal mTORC1 signaling in wild-type cells. PIP4kγ was phosphorylated by mTORC1 and associated with the complex. Phosphorylated PIP4kγ was enriched in light microsomal vesicles, whereas the unphosphorylated form was enriched in heavy microsomal vesicles associated with the Golgi. Furthermore, basal mTORC1 signaling was enhanced by overexpression of an unphosphorylated wild-type PIP4kγ and phosphorylation-defective mutant and decreased by overexpression of a phosphorylation mimetic mutant. Together these results demonstrate that PIP4kγ and mTORC1 interact in a self-regulated feedback loop to maintain low and tightly regulated mTORC1 activation during starvation.
HostingRepository	PRIDE
AnnounceDate	2016-05-04
AnnouncementXML	Submission_2016-05-04_07:12:21.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD001340
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Deborah Sarkes
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	Oxidation; Phospho; Carbamidomethyl
Instrument	LTQ Orbitrap XL

Revision	Datetime	Status	ChangeLog Entry
0	2014-09-18 00:22:47	ID requested
⏵ 1	2016-05-04 07:12:22	announced

Mackey AM, Sarkes DA, Bettencourt I, Asara JM, Rameh LE, is a substrate for mTORC1 that maintains basal mTORC1 signaling during starvation. Sci Signal, 7(350):ra104(2014) [pubmed]

curator keyword: Biomedical, Biological

submitter keyword: PIP4kγ, mTORC1, phosphoinositide, PIP4k, Phossphatidylinositol-5-phosphate 4-kinase

Lucia E. Rameh
contact affiliation	Boston University School of Medicine Department of Medicine Boston, MA 02118 USA
contact email	rameh@bu.edu
lab head
Deborah Sarkes
contact affiliation	BBRI
contact email	dasark1@yahoo.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD001340
     1. Label: PRIDE project
     2. Name: PIP4kγ is a substrate for mTORC1