A novel pH-dependent membrane peptide that binds to EphA2 and inhibits cell migration

• DOI: 10.7554/elife.36645
• Publication Date: 2018-09-17T12:00:55Z
• Authors: Daiane S Alves; Justin M Westerfield; Xiaojun Shi; Vanessa P Nguyen; Katherine M Stefa...; Kristen R Booth; Soyeon Kim; Jennifer Morrell-...; Bing-Cheng Wang; Steven M Abel; Adam W Smith; Francisco N Barrera
• Keywords: EPH receptor A2; Cell membrane

Misregulation of the signaling axis formed by receptor tyrosine kinase (RTK) EphA2 and its ligand, ephrinA1, causes aberrant cell-cell contacts that contribute to metastasis. Solid tumors are characterized an acidic extracellular medium. We intend take advantage this tumor feature design new molecules specifically target tumors. created a novel pH-dependent transmembrane peptide, TYPE7, altering sequence domain EphA2. TYPE7 is highly soluble interacts with surface lipid membranes at neutral pH, while acidity triggers insertion. binds endogenous reduces Akt phosphorylation cell migration as effectively ephrinA1. Interestingly, we found large differences in juxtamembrane extent clustering when comparing activation This work shows it possible pH-triggered membrane peptides activate RTK gain insights on mechanism.