Dataset Information

Activating Mutations in PIK3CA result in Widespread Modulation of the Tyrosine Phosphoproteome

ABSTRACT: 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.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Akhilesh Pandey

LAB HEAD: Akhilesh Pandey

PROVIDER: PXD001460 | Pride | 2018-10-24

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	PIK3CA_Total_proteome-01.msf	Msf
	PIK3CA_Total_proteome-01.pep.xml	Pepxml
	PIK3CA_Total_proteome_1.raw	Raw
	PIK3CA_Total_proteome_10.raw	Raw
	PIK3CA_Total_proteome_11.raw	Raw

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Activating Mutations in PIK3CA Lead to Widespread Modulation of the Tyrosine Phosphoproteome.

Zahari Muhammad Saddiq MS Wu Xinyan X Blair Brian G BG Pinto Sneha M SM Nirujogi Raja S RS Jelinek Christine A CA Malhotra Radhika R Kim Min-Sik MS Park Ben Ho BH Pandey Akhilesh A

Journal of proteome research 20150820 9

The human oncogene PIK3CA is frequently mutated in human cancers. Two hotspot mutations in PIK3CA, E545K and H1047R, have been shown to regulate widespread signaling events downstream of AKT, leading to increased cell proliferation, growth, survival, and motility. We used quantitative mass spectrometry to profile the global phosphotyrosine proteome of isogenic knock-in cell lines containing these activating mutations, where we identified 824 unique phosphopeptides. Although it is well understood ...[more]

PMID: 26267517

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