The Under-Appreciated Promiscuity of the Epidermal Growth Factor Receptor Family

Kennedy, Sean P.; Hastings, Jordan F.; Han, Jeremy Z. R.; Croucher, David R.

doi:10.3389/fcell.2016.00088

Cited by 58 publications

(54 citation statements)

References 102 publications

(173 reference statements)

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“…There is corroborating evidence that Eps8 expression facilitates neural cell motility; in rat neural cell lines and in SVZ explants Eps8 has been shown to function in NRG1-Erb4 stimulated migration (Fregnan et al 2011). Erb4 is a EGFR family receptor, and the members of this family signal through very similar transduction pathways likely to include Eps8 (Kennedy et al 2016). Moreover, the regulation of Eps8 in NPCs provides a likely mechanism underlying our previously reported decrease of Nestin expressing cells in neurosphere cultures from mice lacking Hnrnpab.…”

Section: Hnrnpab Regulates Cell Motility and Eps8 Gene Expression In supporting

confidence: 66%

Hnrnpab regulates neural cell motility through transcription of Eps8

Lampasona

Czaplinski

2018

RNA

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Cell migration requires a complicated network of structural and regulatory proteins. Changes in cellular motility can impact migration as a result of cell-type or developmental stage regulated expression of critical motility genes. Hnrnpab is a conserved RNA-binding protein found as two isoforms produced by alternative splicing. Its expression is enriched in the subventricular zone (SVZ) and the rostral migratory stream within the brain, suggesting possible support of the migration of neural progenitor cells in this region. Here we show that the migration of cells from the SVZ of developing Hnrnpab −/− mouse brains is impaired. An RNA-seq analysis to identify Hnrnpab-dependent cell motility genes led us to Eps8, and in agreement with the change in cell motility, we show that Eps8 is decreased in Hnrnpab −/− SVZ tissue. We scrutinized the motility of Hnrnpab −/− cells and confirmed that the decreases in both cell motility and Eps8 are restored by ectopically coexpressing both alternatively spliced Hnrnpab isoforms, therefore these variants are surprisingly nonredundant for cell motility. Our results support a model where both Hnrnpab isoforms work in concert to regulate Eps8 transcription in the mouse SVZ to promote the normal migration of neural cells during CNS development.

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Section: Hnrnpab Regulates Cell Motility and Eps8 Gene Expression In supporting

confidence: 66%

Hnrnpab regulates neural cell motility through transcription of Eps8

Lampasona

Czaplinski

2018

RNA

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“…Accordingly, a number of therapeutic approaches have been devised to target RTK activity, either through neutralizing antibodies or small molecule kinase inhibitors. As a general therapeutic mechanism, targeting RTK activity will usually elicit a strong initial response, but relapse invariably occurs due to a number of avenues of therapeutic resistance (Kennedy et al, ).…”

Section: Potential Applications For Modelling Of Matrix Signallingmentioning

confidence: 99%

The extracellular matrix as a key regulator of intracellular signalling networks

Hastings

Skhinas

Fey

et al. 2018

British J Pharmacology

159

120

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The extracellular matrix (ECM) is a salient feature of all solid tissues within the body. This complex, acellular entity is composed of hundreds of individual molecules whose assembly, architecture and biomechanical properties are critical to controlling the behaviour and phenotype of the different cell types residing within tissues. Cells are the basic unit of life and the core building block of tissues and organs. At their simplest, they follow a set of rules, governed by their genetic code and effected through the complex protein signalling networks that these genes encode. These signalling networks assimilate and process the information received by the cell to control cellular decisions that govern cell fate. The ECM is the biggest provider of external stimuli to cells and as such is responsible for influencing intracellular signalling dynamics. In this review, we discuss the inclusion of ECM as a central regulatory signalling sub-network in computational models of cellular decision making, with a focus on its role in diseases such as cancer. LINKED ARTICLES: This article is part of a themed section on Translating the Matrix. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.1/issuetoc.

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“…At the very least, we have shown that affinity values from the original publications were derived from data and methods causing serious inaccuracies. This data has had a wide-reaching effect in many areas of SH2 domain research: the data has been used to draw specific conclusions about SH2 domain biology such as identification of EGFR recruitment targets (33), to explain quantitative differences in RTK signaling (9), and as evidence to understand the promiscuity of EGFR tail binding (34). In addition, this work has been used to guide experimental design by filtering potential binding proteins by affinity (35), to reconcile confusing experimental results (36), and to guide new experimental hypothesis testing (37).…”

Section: Discussionmentioning

confidence: 99%

New analysis pipeline for high-throughput domain-peptide affinity experiments improves SH2 interaction data

Ronan

Garnett

Naegle

2020

Preprint

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Protein domain interactions with short linear peptides, such as Src homology 2 (SH2) domain interactions with phosphotyrosinecontaining peptide motifs (pTyr), are ubiquitous and important to many biochemical processes of the cell -both in their central importance to cell physiology, and to the sheer scale of possible interactions. The desire to map and quantify these interactions has resulted in the development of increased throughput quantitative measurement techniques, such as microarray or plate-based fluorescence polarization assays. For example, in the last 15 years, experiments have progressed from measuring single interactions to having covering 500,000 of the 5.5 million possible SH2-pTyr interactions in the human proteome. However, high variability in affinity measurements and disagreements about positive interactions between published datasets led us to re-evaluate the analysis pipelines of published SH2-pTyr datasets. We identified several opportunities for improving the identification of positive and negative interactions, and the accuracy of affinity measurements. These methods account for protein aggregation and degradation, and use model fitting and evaluation that are more appropriate for the non-linear behavior of binding interaction data. In addition to improve affinity accuracy, and increased certainty in negative interactions, we find the reanalyzed data results in significantly improved classification of binding vs non-binding when using machine learning techniques, suggesting improved coherence in the reanalyzed datasets. In addition to providing the revised dataset, we propose this new analysis pipeline and necessary protein activity controls should be part of the design process of many such high-throughput biochemical measurements.

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The Under-Appreciated Promiscuity of the Epidermal Growth Factor Receptor Family

Cited by 58 publications

References 102 publications

Hnrnpab regulates neural cell motility through transcription of Eps8

Hnrnpab regulates neural cell motility through transcription of Eps8

The extracellular matrix as a key regulator of intracellular signalling networks

New analysis pipeline for high-throughput domain-peptide affinity experiments improves SH2 interaction data

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