Mediators of Inflammation / 2018 / Article / Fig 2

Review Article

Role of Epidermal Growth Factor Receptor (EGFR) and Its Ligands in Kidney Inflammation and Damage

Figure 2

Different EGFR signaling systems in the inflammatory process: (A) direct ligand-receptor activation: the first step for the direct activation of EGFR begins with the binding of the ligand to the receptor. In general, EGFR ligands are located as inactive transmembrane precursors, which, in order to bind to their receptor, need to undergo proteolytic processing and be released as soluble ligands into the extracellular medium. This proteolytic processing is carried out by metalloproteases/disintegrins of the ADAM family. (B) Indirect ligand-receptor activation/transactivation: this process is triggered by the binding of molecules such as Ang II, thrombin, and ET1 to their specific receptor. After this binding, the release of second messengers is induced, such as intracellular Ca2+, ROS, and certain protein kinases such as PKC, which induces activation of metalloproteases/disintegrins of the family of ADAMs. After EGFR ligand interaction, the receptor undergoes a conformational change inducing the formation of homo- or heterodimers. Then, the intracellular domain is activated in its tyrosine residues by phosphorylation, promoting the autophosphorylation of these same residues in their homologue. Phosphorylated residues in turn serve as a binding site for certain intracellular kinases that are capable of activating EGFR independently to MMPs, as in the case of the SRC kinase.

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