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A novel succinyl dipeptide stimulates directed cell migration by modulating protein kinase C activity
Author(s) -
Mascardo Renato N.,
Thompson Wayne,
Gallo Mary Ann,
Chambers Timothy C.,
Eilon Gabriel
Publication year - 1990
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041420225
Subject(s) - protein kinase c , cytosol , endothelial stem cell , phorbol , protein kinase a , phosphorylation , microbiology and biotechnology , cell culture , kinase , tetradecanoylphorbol acetate , biochemistry , biology , chemistry , enzyme , in vitro , genetics
In determining the mechanism of the chemokinetic action of the thiol protease inhibitor, E‐64, in endothelial cell monolayers subjected to wounding, we synthesized succinyl‐leucyl‐agmatine (SLA), an analogue of E‐64 that lacked the epoxy group and protease inhibitory effect. We observed that this analogue retained its chemokinetic effect on wounded endothelial cells. Its stimulatory action on en‐dothelial cell polarization response to wounding was rapid and associated with directed cell migration. Furthermore, its effect on cellular polarization was blocked by protein kinase C (PKC) inhibitors and mimicked by pharmacologic agents that stimulated PKC activity. To determine if SLA's chemokinetic action was mediated by protein kinase C activation, we compared the effects of SLA and the tumor promoter phorbol myristate acetato (PMA) on the translocation of PKC activity in endothelial cells. We observed that both SLA and PMA induced the translocation of PKC activity from the cytosolic to the particulate fraction of the cells. We also observed that both SLA and PMA induced the phosphorylation of two proteins (M r 23.4 and 36.5 kDa) in intact 32 P‐labeled cells. Thus, SLA stimulates the endothelial cell locomotor response to wounding by stimulating PKC activity.