Figure 1.

Interactions of tissue kallikrein (KLK1), kallikrein-related peptidases (KLK5 and KLK7) and kinin receptors in the human epidermis. Kinins are formed in the skin by the enzymatic action of tissue kallikrein (KLK1) on kininogens; once formed, bradykinin, a kinin B2 receptor (B2R) agonist, is hydrolyzed by carboxypeptidases N and M to produce kinin B1 receptor (B1R) agonists. Both type of receptors activate signaling pathways (protein tyrosine phosphorylation, ERK1/2, PKC, cFos, NF-κB and/or PI3K/Akt) associated to the differentiation program of human keratinocytes; epidermal growth factor receptor (EGFR) transactivation is also involved. Keratinocyte differentiation can be monitored by the appearance of several protein markers such as involucrin, cytokeratin 10 and profilaggrin. KLK5 and KLK7 participate in desquamation of the superficial epidermal layers.