PXD001460

PXD001460 is an original dataset announced via ProteomeXchange.

Title	Activating Mutations in PIK3CA result in Widespread Modulation of the Tyrosine Phosphoproteome
Description	The human oncogene PIK3CA is frequently mutated in human cancers. The two hotspot mutations in PIK3CA, E545K and H1047R, have been shown to regulate widespread signaling events downstream of AKT. However, the impact of these activating mutations on the tyrosine phosphorylation signaling in the cell has not been studied. Here, we performed a global phosphotyrosine profiling using isogenic knockin cell lines containing these activating mutations. We identified 824 unique phosphopeptides from 308 proteins. We found a surprisingly widespread modulation of tyrosine phosphorylation levels of proteins in the knockin mutant cells, with many of the regulated proteins involved in important biological processes, including those in the cytoskeletal migration pathways and kinase regulated signaling. We observed a widespread modulation of the tyrosine kinome, with 24 of the tyrosine kinases showing either upregulation or downregulation in phosphorylation levels. Many of the regulated phosphosites that we identified were located in the kinase domain or the canonical activating sites, indicating that the kinases were active and hence their downstream signaling pathways. Our study thus shows that the activating mutations in PIK3CA result in widespread tyrosine signaling regulation, in addition to the serine/threonine signaling pathways activated by the canonical PI3K-AKT axis.
HostingRepository	PRIDE
AnnounceDate	2018-10-24
AnnouncementXML	Submission_2018-10-24_08:05:42.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Akhilesh Pandey
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; isotope labeled residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2014-11-04 01:50:50	ID requested
⏵ 1	2018-10-24 08:05:43	announced

Zahari MS, Wu X, Blair BG, Pinto SM, Nirujogi RS, Jelinek CA, Malhotra R, Kim MS, Park BH, Pandey A, Activating Mutations in PIK3CA Lead to Widespread Modulation of the Tyrosine Phosphoproteome. J Proteome Res, 14(9):3882-3891(2015) [pubmed]

curator keyword: Biomedical

submitter keyword: Human, PIK3CA, breast cancer, phosphoproteomics, tyrosine

Akhilesh Pandey
contact affiliation	McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland 21205 USA
contact email	pandey@jhmi.edu
lab head
Akhilesh Pandey
contact affiliation	Johns Hopkins University
contact email	pandey@jhmi.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD001460
     1. Label: PRIDE project
     2. Name: Activating Mutations in PIK3CA result in Widespread Modulation of the Tyrosine Phosphoproteome