  The primary activation of the epidermal growth factor receptor (EGFR) has
become a prominent target for molecular therapies against several forms of
cancer. But despite considerable progress during the last years, many of its
aspects remain poorly understood. Experiments on lateral spreading of receptor
activity into ligand-free regions challenge the current standard models of EGFR
activation. Here, we propose and study a theoretical model, which explains
spreading into ligand-free regions without introducing any new, unknown kinetic
parameters. The model exhibits bistability of activity, induced by a generic
reaction mechanism, which consists of activation via dimerization and
deactivation via a Michaelis-Menten reaction. It possesses slow propagating
front solutions and faster initial transients. We analyze relevant experiments
and find that they are in quantitative accordance with the fast initial modes
of spreading, but not with the slow propagating front. We point out that
lateral spreading of activity is linked to pathological levels of persistent
receptor activity as observed in cancer cells and exemplify uses of this link
for the design and quick evaluation of molecular therapies targeting primary
activation of EGFR.
