Dermokine-β impairs ERK signaling through direct binding to GRP78

► Treatment of keratinocytes or skin tumor cells with recombinant dermokine-β inhibited phosphorylation of ERK1/2. ► Exposure of keratinocytes to dermokine-β stimulated its gene expression. ► Carboxyl-terminus domain of dermokine-β confers its functions. ► Dermokine-β physically interacted with GRP78. ► Down-regulation of GRP78 expression abrogated the functions of dermokine-β.