title: Engineered epidermal growth factor mutants with faster binding on-rates correlate with enhanced receptor activation.
abstract: Receptor tyrosine kinases (RTKs) regulate critical cell signaling pathways, yet the properties of their cognate ligands that influence receptor activation are not fully understood. There is great interest in parsing these complex ligand-receptor relationships using engineered proteins with altered binding properties. Here we focus on the interaction between two engineered epidermal growth factor (EGF) mutants and the EGF receptor (EGFR), a model member of the RTK superfamily. We found that EGF mutants with faster kinetic on-rates stimulate increased EGFR activation compared to wild-type EGF. These findings support previous predictions that faster association rates correlate with enhanced receptor activity.
authors: Department of Bioengineering, Cancer Center, Bio-X Program, Stanford University, Stanford, CA 94305, USA.
authors: Jennifer L
authors: JL
authors: Lahti
authors: Bertrand H
authors: BH
authors: Lui
authors: Stayce E
authors: SE
authors: Beck
authors: Stephen S
authors: SS
authors: Lee
authors: Daphne P
authors: DP
authors: Ly
authors: Michael T
authors: MT
authors: Longaker
authors: George P
authors: GP
authors: Yang
authors: Jennifer R
authors: JR
authors: Cochran
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D002460:Cell Line; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015151:Immunoblotting; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D011485:Protein Binding; D015202:Protein Engineering; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D020349:Surface Plasmon Resonance
chemical_list: D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D050505:Mutant Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases