Quantification of ErbB Network Proteins in Three Cell Types Using Complementary Approaches Identifies Cell-General and Cell-Type-Specific Signaling Proteins

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).