Epidermal Growth Factor Receptor Activation Paper Example

Introduction

Epidermal growth factor receptor can be activated by the ionizing radiation, an act which leads to a transcription event. As noted by Dr. Duronio 15.45, Epidermal growth factor receptor plays a critical role in the cell proliferation regulation. In this regard, it is evident that EGFR belongs to the ErbB family which hosts the receptor Tyr kinases [1]. Such proteins with a transmembrane undergo activation from the extracellular ligands exhibited by the EGF family leading to signaling events of a cytoplasmic nature. Besides, repeated and single radiation exposure lead to a response of cellular proliferative nature in vitro. Ionizing radiation of a range of one to five Gy is associated with the activation of EGFR, an action which affects the pathway for mitrogen- activated protein kinase [2]. In this scenario, p90RSK, downstream effector for MAPK and factors for the phosphorylate transcription participate in the cell proliferation.

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Pro-death Environment

The presence of advanced medical practices has led to the exposure of cells to radiation. Besides, the experiments involving the use of heavy charged neutrons and ions contribute to the cells' exposure to radiation. Dr Duronio records that high level of oxidants such as ultraviolet light and X-rays make up negative signals which are pro-apoptotic as they eliminate toxic cells. Such scenarios initiate a pro-death environment where cells die as noted by Daly [3]. In this case, the cells react to the radiation by lethality where they undergo destruction. Radiation activates the family proteins of the proapoptotic BCL-2, inducing SMAC or cytochrome release [4]. Subsequently, the cytochrome c triggers the development of apoptosome complex containing APAF-1, caspase 9 and cytochrome c. Also, SMAC perpetuates apoptosis as it binds to XIAP leading to the production of apoptosis' downstream activation and caspase 9.

Similarities and Differences of the Signaling Networks

These two signaling networks bear similarities and differences when protein-protein binding and post-translational modification are considered. One of the similarities between the two signaling networks is that protein-protein interactions regulate both networks. It should be noted that protein-protein interaction show the physical contact regarding more molecules of high specificity that results from biochemical events. During transcription, protein phosphate 1 and proteins ku70/80 are transported whereby an increase of the kinase which is DNA dependent leads to the manufacturing of protein complexes for DNA end binding [5]. It should be noted that the Ku antigen contains 82 and 70 Kda subunits which bind with the ends of the DNA that are double-stranded. After binding, the heterodimer in the Ku 70/80 promote the kinase activity exhibited by the DNA-PKcs and the subunit of the protein kinase [6]. In the events of ionization, p53-binding protein is activated by Ku autoantigen. During the events resulting to genome damage such as exposure to gamma radiation, pathways involved in the repair mechanisms for DNA are induced. In this case, the ku80 and ku70 form a complex which activates DNA-PKcs.

However, both signaling networks differ on the functioning of the post-translational modifications. For example, the main aim of the post-translational modifications in the epidermal growth factor receptor is to modulate the trafficking and signaling of EGFR [7]. This is followed by internalization of EGFR by the endocytosis. Besides, the recycling and EGFR internalization occur as a counteraction of stresses which are involved in the activation of the p38 MAP kinase Conversely, in the apoptosis triggered by radiation, post-translational modification occurs in p-53 to activate gene transcription and enhance its binding to the promoters found in target genes [8]. In the presence of stress, nuclear export and degradation of p53 are inhibited while the nuclear import activities are enhanced.

References

Hubbard S, & Miller W. Receptor tyrosine kinases: mechanisms of activation and signaling. Current Opinion in Cell Biology. 2007; 19(2): 117-23.

Hagan M, Wang L, Hanley J, Park J, Dent P. Ionizing radiation-induced mitogen-activated protein (MAP) Kinase activation in DU145 prostate carcinoma cells: MAP kinase inhibition enhances radiation-induced cell killing and G2/M-phase arrest. Radiat Res. 2000; 153(4): 371-83.

Daly M. Death by protein damage in irradiated cells. DNA Repair. 2012;11(2012): 12-21.

Li J, Wang Y, Du L, Xu C, Cao J, Wang Q, et al. (2013). Radiation-induced cytochrome c release and the neuroprotective effects of the pan-caspase inhibitor z-VAD-fmk in the hypoglossal nucleus. Experimental and Therapeutic Medicine. 2013; 7(2): 383-388.

Diggle C, Bentley J, Knowles M, Kiltie A. Inhibition of double-strand break nonhomologous end-joining by cisplastin adducts in human cell extracts. Nucleic Acids Research. 2005; 33(8): 2531-2539.

Brown K, Lataxes T, Shangary S, Mannino J, Giardina J, Chen J, Baskaran, R. Ionizing radiation exposure results in up-regulation of ku70 via a p53/Ataxia-Telangiectasia-mutated protein-dependent mechanism. The Journal of Biological Chemistry. 2000;275: 6651-6656.

Tong J, Taylor P, Moran M. Proteomic analysis of the epidermal growth factor receptor (EGFR) interactome and post-translational modifications associated with receptor endocytosis in response to EGF and stress. Mol Cell Proteomics. 2014; 13(7): 1644-58.

Gu B, Zhu W. Surf the post-translational modification network of p53 regulation. International Journal of Biological Sciences, 2012;8(5): 672-84.