title: Consequences of replacing EGFR juxtamembrane domain with an unstructured sequence.
abstract: EGFR is the best studied receptor tyrosine kinase. Yet, a comprehensive mechanistic understanding of EGFR signaling is lacking, despite very active research in the field. In this paper, we investigate the role of the juxtamembrane (JM) domain in EGFR signaling by replacing it with a (GGS)(10) unstructured sequence. We probe the effect of this replacement on (i) EGFR phosphorylation, (ii) EGFR dimerization and (iii) ligand (EGF) binding. We show that the replacement of EGFR JM domain with a (GGS)(10) unstructured linker completely abolishes the phosphorylation of all tyrosine residues, without measurable effects on receptor dimerization or ligand binding. Our results suggest that the JM domain does not stabilize the inactive EGFR dimer in the absence of ligand, and is likely critical only for the last step of EGFR activation, the ligand-induced transition from the inactive to active dimer.
authors.affiliation: Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Lijuan
authors.initials: L
authors.lastname: He
authors.forename: Kalina
authors.initials: K
authors.lastname: Hristova
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D010766:Phosphorylation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization
chemical_list: D008024:Ligands; D004815:Epidermal Growth Factor; D066246:ErbB Receptors