Dataset Information

Different Epidermal Growth Factor Receptor (EGFR) Agonists Produce Unique Signatures for the Recruitment of Downstream Signaling Proteins.

ABSTRACT: The EGF receptor can bind seven different agonist ligands. Although each agonist appears to stimulate the same suite of downstream signaling proteins, different agonists are capable of inducing distinct responses in the same cell. To determine the basis for these differences, we used luciferase fragment complementation imaging to monitor the recruitment of Cbl, CrkL, Gab1, Grb2, PI3K, p52 Shc, p66 Shc, and Shp2 to the EGF receptor when stimulated by the seven EGF receptor ligands. Recruitment of all eight proteins was rapid, dose-dependent, and inhibited by erlotinib and lapatinib, although to differing extents. Comparison of the time course of recruitment of the eight proteins in response to a fixed concentration of each growth factor revealed differences among the growth factors that could contribute to their differing biological effects. Principal component analysis of the resulting data set confirmed that the recruitment of these proteins differed between agonists and also between different doses of the same agonist. Ensemble clustering of the overall response to the different growth factors suggests that these EGF receptor ligands fall into two major groups as follows: (i) EGF, amphiregulin, and EPR; and (ii) betacellulin, TGF?, and epigen. Heparin-binding EGF is distantly related to both clusters. Our data identify differences in network utilization by different EGF receptor agonists and highlight the need to characterize network interactions under conditions other than high dose EGF.

SUBMITTER: Ronan T

PROVIDER: S-EPMC4786695 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Different Epidermal Growth Factor Receptor (EGFR) Agonists Produce Unique Signatures for the Recruitment of Downstream Signaling Proteins.

Ronan Tom T Macdonald-Obermann Jennifer L JL Huelsmann Lorel L Bessman Nicholas J NJ Naegle Kristen M KM Pike Linda J LJ

The Journal of biological chemistry 20160119 11

The EGF receptor can bind seven different agonist ligands. Although each agonist appears to stimulate the same suite of downstream signaling proteins, different agonists are capable of inducing distinct responses in the same cell. To determine the basis for these differences, we used luciferase fragment complementation imaging to monitor the recruitment of Cbl, CrkL, Gab1, Grb2, PI3K, p52 Shc, p66 Shc, and Shp2 to the EGF receptor when stimulated by the seven EGF receptor ligands. Recruitment of ...[more]

PMID: 26786109

Similar Datasets

Project description:ObjectiveTest the hypothesis that exercise and pharmacological cardiac stressors create different electrical ischemic signatures.IntroductionCurrent clinical stress tests for detecting ischemia lack sensitivity and specificity. One unexplored source of the poor detection is whether pharmacological stimulation and regulated exercise produce identical cardiac stress.MethodsWe used a porcine model of acute myocardial ischemia in which animals were instrumented with transmural plunge-needle electrodes, an epicardial sock array, and torso arrays to simultaneously measure cardiac electrical signals within the heart wall, the epicardial surface, and the torso surface, respectively. Ischemic stress via simulated exercise and pharmacological stimulation were created with rapid electrical pacing and dobutamine infusion, respectively, and mimicked clinical stress tests of five 3-minute stages. Perfusion to the myocardium was regulated by a hydraulic occluder around the left anterior descending coronary artery. Ischemia was measured as deflections to the ST-segment on ECGs and electrograms.ResultsAcross eight experiments with 30 (14 simulated exercise and 16 dobutamine) ischemic interventions, the spatial correlations between exercise and pharmacological stress diverged at stage three or four during interventions (p<0.05). We found more detectable ST-segment changes on the epicardial surface during simulated exercise than with dobutamine (p<0.05). The intramyocardial ischemia formed during simulated exercise had larger ST40 potential gradient magnitudes (p<0.05).ConclusionWe found significant differences on the epicardium between cardiac stress types using our experimental model, which became more pronounced at the end stages of each test. A possible mechanism for these differences was the larger ST40 potential gradient magnitudes within the myocardium during exercise. The presence of microvascular dysfunction during exercise and its absence during dobutamine stress may explain these differences.

Dataset Information

Different Epidermal Growth Factor Receptor (EGFR) Agonists Produce Unique Signatures for the Recruitment of Downstream Signaling Proteins.

Publications

Different Epidermal Growth Factor Receptor (EGFR) Agonists Produce Unique Signatures for the Recruitment of Downstream Signaling Proteins.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets