I. Hoffmann et al., Activation of ErbB2 receptor tyrosine kinase supports invasion of endothelial cells by Neisseria meningitidis, J CELL BIOL, 155(1), 2001, pp. 133-143
ErbB2 is a receptor tyrosine kinase belonging to the family of epidermal gr
owth factor (EGF) receptors which is generally involved in cell differentia
tion, proliferation, and tumor growth, and activated by heterodimerization
with the other members of the family. We show here that type IV pilus-media
ted adhesion of Neisseria meningitidis onto endothelial cells induces tyros
yl phosphorylation and massive recruitment of ErbB2 underneath the bacteria
l colonies. However, neither the phosphorylation status nor the cellular lo
calization of the EGF receptors, ErbB3 or ErbB4, were affected in infected
cells. ErbB2 phosphorylation induced by N. meningitidis provides docking si
tes for the kinase src and leads to its subsequent activation. Specific inh
ibition of either ErbB2 and/or src activity reduces bacterial internalizati
on into endothelial cells without affecting bacteria-induced actin cytoskel
eton reorganization or ErbB2 recruitment. Moreover, inhibition of both acti
n polymerization and the ErbB2/src pathway totally prevents bacterial entry
. Altogether, our results provide new insight into ErbB2 function by bringi
ng evidence of a bacteria-induced ErbB2 clustering leading to src kinase ph
osphorylation and activation. This pathway, in cooperation with the bacteri
a-induced reorganization of the actin cytoskeleton, is required for the eff
icient internalization of N. meningitidis into endothelial cells, an essent
ial process enabling this-pathogen to cross host cell barriers.