Pemphigus, p38MAPK, acantholysis and apoptosis. Two sequential peaks of p38MAPK activation are observed when keratinocytes are exposed to either PV or PF IgG. (a) Pemphigus IgG binds to dsg and biases the equilibrium of desmosome assembly/disassembly towards disassembly which is linked by an, as yet, undefined mechanism towards activation of p38MAPK. Subsequent p38 dependent alterations in the cell state include RhoA inactivation, dsg endocytosis, HSP27 phosphorylation, keratin intermediate filament retraction, actin, and loss of cell-cell adhesion (acantholysis). (b) A second late peak of p38 activity is observed that is likely a stress response signal induced by loss of cell-cell adhesion and leads to activation of proapoptotic pathways including caspase-3 activation.
