Leukoregulin-induced translocation of protein kinase C activity in K562 cells.
Leukoregulin's effect on biochemical pathways involving Ca2+ was assessed in K562 erythroleukemia cells in which the antitumor lymphokine induces a rapidly reversible increase in plasma membrane permeability. Leukoregulin exposure activates protein kinase C but does not alter levels of phosphoinositol metabolites, calmodulin or cAMP. The activation pattern of protein kinase C differs from that induced by phorbol myristic acid (PMA), a potent activator of protein kinase C. PMA-induced translocation of protein kinase C from the cytosol to the plasma membrane is maximal by 2 min after addition of PMA whereas after leukoregulin treatment protein kinase C translocation reaches a maximum at 2 h. This suggests that leukoregulin activates protein kinase C via a non-classical phosphoinositol pathway as opposed to direct binding to protein kinase C as occurs with PMA. The temporal kinetics of the protein kinase C translocation and the increase in membrane permeability induced by leukoregulin are similar suggesting that phosphorylation of a membrane protein may be involved in the target cell destabilization of the plasma membrane by this lymphokine.
Barnett
S C
SC
Laboratory of Biology, National Cancer Institute, Bethesda, Maryland 20892.
Evans
C H
CH
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002147:Calmodulin / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000201:enzymology*; D008222:Lymphokines / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D002147:Calmodulin; D008222:Lymphokines; D010716:Phosphatidylinositols; C044162:leukoregulin; D000242:Cyclic AMP; D011493:Protein Kinase C