The activation of inactive membrane-associated protein kinase C is associated with DMSO-induced erythroleukemia cell differentiation.
The rapid redistribution of cytosolic protein kinase C (PKC) to membranes and its subsequent proteolytic activation to PKM have been implicated in the DMSO/HMBA-induced differentiation of murine erythroleukemia (MEL) cells. However, DMSO was found not to induce detectable changes in PKC distribution in a MEL cell subline (MEL1) which differentiated normally in response to the agent. Nevertheless, the differentiation of MEL1 cells appeared dependent on an early PKC-related event because hemoglobinization was partially blocked by the PKC inhibitor H-7 added to cells within the first 2 h after DMSO induction. Indeed, a rapid (15-60 min) increase in membrane PKC activity was detected in DMSO-treated MEL1 cells using a novel method which quantitates the amount of 'active' PKC in intact membranes. This transient PKC increase resulted from the activation of 'inactive' enzyme already associated with membranes, and not from the translocation of cytosolic PKC. Conventional PKC assays cannot distinguish between active and inactive membrane PKC pools. DMSO also activated inactive membrane PKC in HL-60 cells, but not in S49T-lymphoma and WEHI-231 B-lymphoma cells which do not differentiate in response to DMSO. The results suggest that a rapid and transient increase in membrane PKC activity may be an important early step in DMSO-induced differentiation of erythroleukemia cells.
Chakravarthy
B R
BR
Institute for Biological Sciences, National Research Council of Canada, Ottawa.
Tremblay
R
R
Macdonald
P
P
Krsmanovic
V
V
Whitfield
J F
JF
Durkin
J P
JP
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002462:Cell Membrane / Q000201:enzymology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004789:Enzyme Activation; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D011493:Protein Kinase C / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D011493:Protein Kinase C; D004121:Dimethyl Sulfoxide