Serine protease inhibitors of the Kazal-type 9 (SPINK9) is a keratinocyte-derived cationic peptide that is found most abundantly in the upper layers of the palmar-plantar epidermis. In vitro, the peptide displays the capacity to inhibit specifically kallikrein-related peptidase 5 (KLK5). Here, we report that cells expressing SPINK9 secrete the peptide constitutively. Recombinant SPINK9 (rSPINK9) provoked transactivation of the EGFR in human keratinocytes, resulting in efficient downstream triggering of cell migration. Transactivation occurred via functional upregulation of a disintegrin and metalloproteases (ADAMs), as evidenced by suppression with a metalloproteinase inhibitor and an EGFR-blocking antibody. SPINK9 preparations isolated from human skin also displayed EGFR-transactivating capacity. The classical purinergic receptor antagonists oxidized ATP and pyridoxalphosphate-6-azophenyl-2',4',-disulfonic acid effectively suppressed EGFR transactivation by rSPINK9, indicating that in analogy to what has recently been reported for the cationic antimicrobial peptides cathelicidin LL-37 and bee venom melittin, purinergic receptors have an essential bridging role in promoting the upregulation of ADAM function by the cationic peptide. SPINK9 could represent an example of how a cationic peptide may subserve multiple and interrelated functions that contribute to the maintenance of the physical and immunological barrier of the skin.

• MeSH
• erbB receptory metabolismus   MeSH
• HEK293 buňky MeSH
• hojení ran MeSH
• inhibitory serinových peptidas Kazalova typu MeSH
• kalikreiny metabolismus   MeSH
• kathelicidiny MeSH
• kationické antimikrobiální peptidy metabolismus   MeSH
• keratinocyty cytologie   MeSH
• klonování DNA MeSH
• lidé MeSH
• metaloproteasy metabolismus   MeSH
• pohyb buněk * MeSH
• proliferace buněk MeSH
• purinergní receptory metabolismus   MeSH
• regulace genové exprese enzymů * MeSH
• rekombinantní proteiny metabolismus   MeSH
• sekreční inhibitory proteinas metabolismus   MeSH
• signální transdukce MeSH
• transfekce MeSH
• viabilita buněk MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• erbB receptory MeSH
• inhibitory serinových peptidas Kazalova typu MeSH
• kalikreiny MeSH
• kathelicidiny MeSH
• kationické antimikrobiální peptidy MeSH
• KLK5 protein, human MeSH Prohlížeč
• metaloproteasy MeSH
• purinergní receptory MeSH
• rekombinantní proteiny MeSH
• sekreční inhibitory proteinas MeSH
• Spink9 protein, human MeSH Prohlížeč