Proposed mechanism of EGFR feedback monomerization upon EGF stimulation.
Malgorzata Kluba
Yves Engelborghs
Johan Hofkens
Hideaki Mizuno
10.1371/journal.pone.0139971.g006
https://plos.figshare.com/articles/figure/_Proposed_mechanism_of_EGFR_feedback_monomerization_upon_EGF_stimulation_/1575196
<p>After EGF challenging, two EGFR monomers associate on the plasma membrane to form an asymmetric dimer. The asymmetric dimer formation activates the kinase domain which transphosphorylates tyrosine residues at the C-termini of the receptor, three of which (pY1173, pY1148, pY992) recruit PLCγ1. EGFR phosphorylates PLCγ1 on Y783 for activation. PLCγ1 hydrolyses PIP<sub>2</sub> forming DAG. DAG activates nPKCs, which phosphorylates PKD at S744 and S748 for activation. PKD causes EGFR phosphorylation at T654 and/or T669 to shift the monomer-dimer equilibrium of liganded EGFR back towards the monomer. The insets show the close-up of the JM part. The two PDB files (2M20, 3GOP) were superimposed and aligned in the JM-A region to obtain presented images.</p>
2015-10-14 04:12:03
EGFR dimer formation
receptor monomerization
monomeric state
feedback loop
pkd
epidermal growth factor receptor
protein kinase D
EGFR Signaling Dimerization
feedback mechanism
juxtamembrane threonine residues
raster image correlation spectroscopy
Signal transduction
dimerization state
oscillatory behavior
Receptor Dimerization
2.5 min