Protein kinase C inhibitors enhance concanavalin a cap formation in polymorphonuclear leukocytes

Abstract

The potent protein kinase C (PKC) inhibitors, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) and staurosporine, significantly enhanced concanavalin A (Con A)-induced cap formation in polymorphonuclear leukocytes (PMNs) from C57BL/6 mice after pretreatment for 30 min at concentrations of 10 μM and 1 nM, respectively. However, neither 10 μM of N-(2-aminoethyl)-5-isoquinolinesulfonamide dihydrochloride (H-9) nor N-(2-guanidinoethyl)-5-isoquinolinesulfonamide hydrochloride (HA1004), which inhibit cyclic nucleotide-dependent protein kinases more effectively than other kinases, affected the capping. Meanwhile, treatment of PMNs with Con A induced the translocation of PKC from the cytosol to the membrane fraction within 5 min, which is considered to be important for the activation of this enzyme. When cells were pretreated with H-7 or straurosporine for 30 min at the concentrations that enhanced the capping, both the cytosolic and the membrane-bound PKC activity was inhibited during the further incubation with Con A. These results suggest that PKC may play an important role in the regulation of Con A-induced cap formation in PMNs.