Icated that EPHA2 formed robust complexes with Src kinase and was mostly serine phosphorylated in

Icated that EPHA2 formed robust complexes with Src kinase and was mostly serine phosphorylated in the lens. RNA sequencing analysis revealed differential expression of a number of cytoskeleton-associated genes in Epha2-mutant and Epha2-null lenses such as shared downregulation of Lgsn and Clic5. Collectively, our data recommend that mutations within the tyrosinekinase domain of EPHA2 lead to lens cell patterning defects and dysregulated expression of various cytoskeleton-associated proteins. Keywords and phrases: lens; ephrin receptor; cell patterning; cytoskeleton; cataractAcademic Editor: Paola Bagnoli Received: 10 August 2021 Accepted: 27 September 2021 Published: 30 September1. Introduction 1st identified as epithelial cell kinase (eck), ephrin type-A receptor 2 (EPHA2) belongs to the Thapsigargin Membrane Transporter/Ion Channel biggest subfamily of receptor tyrosine kinases that have been originally discovered in a human erythropoietin-producing-hepatoma (EPH) cell line [1,2]. EPH receptors and their membrane-bound EPH receptor interacting ligands, or ephrins, play key signaling roles in embryonic improvement like tissue patterning, neurogenesis and vasculogenesis, adult tissue physiology including bone homeostasis and insulin secretion in addition to many illnesses including cancers and neurodegeneration [3]. The mammalian EPH/ephrin receptor subfamily comprises 14 receptors divided into type-A (EPHA1-8, 10) and type-B (EPHB1-5) that preferentially interact with ephrin type-A (EFNA1-5) and type-B (EFNB1-3) ligands, respectively, to elicit forward (receptor-driven) or reverse (ligand-driven) bidirectional signaling in neighboring cells. Like other receptor tyrosine kinases, EPHA2 shares a type-1 (single-pass) transmembrane glycoprotein topology with many functional domains such as an extracellular (N-terminal) ligand binding domain and an intracellular (C-terminal) tyrosine kinase (TK) signaling domain along with a sterile-alpha-motif (SAM) domain implicated in modulating kinase activity and receptor dimerization [6,7]. Canonical forward signaling by EFNA1-EPHA2 frequently promotes cell ell repulsion accompanied byPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.Copyright: 2021 by the authors. Licensee MDPI, Basel, Switzerland. This short article is definitely an open access short article distributed below the terms and situations of your Inventive Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).Cells 2021, 10, 2606. https://doi.org/10.3390/cellshttps://www.mdpi.com/journal/cellsCells 2021, 10,two ofEPHA2 oligomerization, phosphorylation, and kinase U0126 site activation, whereas EPHA2-EFNA1 reverse signaling elicits kinase-independent cell ell adhesion or repulsion according to the specific cellular xtracellular context [8,9]. Furthermore, EPHA2 possesses ligandindependent kinase activity in many cultured tumor cell sorts [8,10] and overexpression of EPHA2 serves both as a prognostic marker and therapeutic target in a variety of human epithelial cancers (e.g., breast, gastric, and lung), glioblastoma, and melanoma, whereas EPHA2 sequence variants have already been associated with susceptibility to Kaposi’s sarcoma [9,11,12]. Additionally, EPHA2 serves as a receptor for the growth element progranulin [13] and many infectious agents which includes oncogenic viruses and fungal pathogens, and is involved in blood rain barrier breakdown in the course of malarial infection [146]. Apart from cancer and infectious illnesses, EPHA2 has been repeatedly linked with.