Icated that EPHA2 formed strong complexes with Src kinase and was mainly serine phosphorylated in the lens. RNA sequencing analysis revealed differential expression of numerous cytoskeleton-associated genes in Epha2-mutant and Epha2-null lenses such as shared downregulation of Lgsn and Clic5. Collectively, our data suggest that mutations inside the tyrosinekinase domain of EPHA2 lead to lens cell patterning defects and dysregulated expression of numerous cytoskeleton-associated proteins. Keywords and phrases: lens; ephrin receptor; cell patterning; cytoskeleton; cataractAcademic Editor: Paola Bagnoli Received: ten August 2021 Accepted: 27 September 2021 Published: 30 September1. Introduction Initial identified as epithelial cell kinase (eck), ephrin type-A receptor two (EPHA2) belongs to the biggest subfamily of receptor tyrosine kinases that were initially 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 including tissue patterning, neurogenesis and vasculogenesis, adult tissue physiology which includes bone homeostasis and insulin secretion together with a variety of illnesses which includes cancers and neurodegeneration [3]. The mammalian EPH/ephrin receptor subfamily comprises 14 receptors divided into type-A (EPHA1-8, ten) 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 several functional domains such as an extracellular (N-terminal) ligand binding domain and an intracellular (C-terminal) tyrosine kinase (TK) signaling domain plus a sterile-alpha-motif (SAM) domain implicated in modulating kinase activity and receptor dimerization [6,7]. Canonical forward signaling by EFNA1-EPHA2 typically promotes cell ell repulsion accompanied byPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional Quizartinib MedChemExpress affiliations.Copyright: 2021 by the authors. ��-Amanitin MedChemExpress Licensee MDPI, Basel, Switzerland. This short article is an open access article distributed beneath the terms and situations in the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ four.0/).Cells 2021, ten, 2606. https://doi.org/10.3390/cellshttps://www.mdpi.com/journal/cellsCells 2021, ten,2 ofEPHA2 oligomerization, phosphorylation, and kinase activation, whereas EPHA2-EFNA1 reverse signaling elicits kinase-independent cell ell adhesion or repulsion depending on the particular cellular xtracellular context [8,9]. Additionally, EPHA2 possesses ligandindependent kinase activity in several cultured tumor cell types [8,10] and overexpression of EPHA2 serves both as a prognostic marker and therapeutic target in different 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]. In addition, EPHA2 serves as a receptor for the growth aspect progranulin [13] and numerous infectious agents including oncogenic viruses and fungal pathogens, and is involved in blood rain barrier breakdown for the duration of malarial infection [146]. Besides cancer and infectious ailments, EPHA2 has been repeatedly linked with.
