2019
DOI: 10.1371/journal.pcbi.1006706
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Modeling cell line-specific recruitment of signaling proteins to the insulin-like growth factor 1 receptor

Abstract: Receptor tyrosine kinases (RTKs) typically contain multiple autophosphorylation sites in their cytoplasmic domains. Once activated, these autophosphorylation sites can recruit downstream signaling proteins containing Src homology 2 (SH2) and phosphotyrosine-binding (PTB) domains, which recognize phosphotyrosine-containing short linear motifs (SLiMs). These domains and SLiMs have polyspecific or promiscuous binding activities. Thus, multiple signaling proteins may compete for binding to a common SLiM and vice v… Show more

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Cited by 8 publications
(5 citation statements)
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“…First, there could be errors in the copy number measure-ments that were used to obtain the cell-specific models. In a recent study, concerns were raised about the accuracy of available data sets (Erickson et al, 2019), including the data set that we used to set abundances of EGFR, Grb2, and Shc1 for the HeLa cell-specific model. Second, as a simplification, we held rate constants for receptor phosphorylation and dephosphorylation fixed across the different cell-specific versions of the model.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…First, there could be errors in the copy number measure-ments that were used to obtain the cell-specific models. In a recent study, concerns were raised about the accuracy of available data sets (Erickson et al, 2019), including the data set that we used to set abundances of EGFR, Grb2, and Shc1 for the HeLa cell-specific model. Second, as a simplification, we held rate constants for receptor phosphorylation and dephosphorylation fixed across the different cell-specific versions of the model.…”
Section: Discussionmentioning
confidence: 99%
“…In addition to Y1068 and Y1173, the model accounts for other tyrosines in EGFR, which are lumped together and labeled YN in the BNGL-formatted model-definition file. The model structure was optimized using model restructuration (reviewed in the supplementary tutorial of Erickson et al, 2019).…”
Section: Mathematical Modelingmentioning
confidence: 99%
“…These rules are directly transformed into systems of ODEs by specific software packages, such as BioNetGen [ 133 , 134 ]. Models that are built in BioNetGen can be integrated by the Network-Free Stochastic Simulator (NFsim) [ 135 , 136 ]. NFsim can use the Gillespie SSA and consider noise, intrinsically present in biological systems, for instance, in transcription factor networks [ 78 ].…”
Section: Mechanistic Modelsmentioning
confidence: 99%
“…Multiple approaches have been used to extract mechanistic insights from mathematical models of network-driven processes. These approaches range from simple tracking of one or multiple species in the network (10)(11)(12)(13)(14) to more complex applications, such as Information Theoretic concepts to estimate the channel capacity between nodes in a network (15)(16)(17)(18)(19)(20). Stoichiometric flux balance analysis methods are perhaps the most widely used approaches to analyze reaction flux in networks (21)(22)(23)(24)(25).…”
Section: Introductionmentioning
confidence: 99%