Role of protein kinases in the in vitro differentiation of human epidermal HaCaT cells.

Different chemicals that specifically and selectively inhibit or activate protein kinases have been used to define the possible roles of these enzymes in the different steps of epidermal differentiation. Using HaCaT keratinocytes as a model, and under conditions in which cell proliferation is minimally affected, we found that tyrosine kinase inhibition leads to an inhibition of early (spinous; keratin k10 expression) and late (granulosum; involucrin expression) differentiation processes. cGMP- and cAMP-dependent protein kinases appear to modulate the transition from spinous to granular differentiation, a process which seems to be negatively controlled by protein phosphatases. Finally, enzymes belonging to the protein kinase C family appear to facilitate the transition from spinous to granular differentiation programmes while inhibiting the early steps of epidermal differentiation.