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J Proteome Res. 2014 Jan 3;13(1):300-13. doi: 10.1021/pr400878x. Epub 2013 Dec 9.

Quantification of ErbB network proteins in three cell types using complementary approaches identifies cell-general and cell-type-specific signaling proteins.

Author information

1
EMBL/CRG Systems Biology Research Unit, ‡Proteomics Unit, §Advanced Light Microscopy Core Facility, Centre for Genomic Regulation (CRG) , Dr. Aiguader 88, 08003 Barcelona, Spain.

Abstract

Relating protein concentration to cell-type-specific responses is one of the remaining challenges for obtaining a quantitative systems level understanding of mammalian signaling. Here we used mass-spectrometry (MS)- and antibody-based quantitative proteomic approaches to measure protein abundances for 75% of a hand-curated reconstructed ErbB network of 198 proteins, in two established cell types (HEK293 and MCF-7) and in primary keratinocyte cells. Comparison with other quantitative studies allowed building a set of ErbB network proteins expressed in all cells and another which are cell-specific and could impart specific properties to the network. As a proof-of-concept of the importance of protein concentration, we generated a small simplified mathematical model encompassing ligand binding, followed by receptor dimerization, activation, and degradation. The model predicts ErbB phosphorylation in HEK293, MCF-7, and keratinocyte cells simply by incorporating cell-type-specific ErbB1, ErbB2, and caveolin-1 abundances but otherwise contains similar rate constants. Altogether, the data provide a resource for protein abundances and localization to be included in larger mathematical models, enabling the generation of cell-type-specific computational models. MS data have been deposited to the ProteomeXchange via PRIDE (with identifier PXD000623) and PASSEL (with identifier PASS00372).

PMID:
24313378
DOI:
10.1021/pr400878x
[Indexed for MEDLINE]

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