Interleukin-2 induces proliferation of T lymphocyte mutants lacking protein kinase C.
We have identified a murine T lymphocyte clone that apparently lacks diacylglycerol- and phospholipid-activated protein kinase C (PKC): cell extracts do not display phosphatidylserine, Ca2+, or phorbol ester-dependent phosphotransferase activity; the enzyme was not detected in immunoblots with PKC-specific antibodies; phorbol ester binding sites are not detectable in intact cells; and activators of PKC do not stimulate proliferation or Na+/H+ exchange in intact cells. Only PKC beta mRNA was detected in normal murine T lymphocytes. The mutant T lymphocytes contained amounts of 4.4 kb PKC beta message similar to those in normal murine lymphocytes, but the 2.9 kb and 1.2 kb messages found in normal lymphocytes were barely detectable. No abnormalities were detected on Southern analysis, suggesting that the abnormality may be at the level of message splicing or stability. Since PKC-deficient cells proliferate in response to the T lymphocyte growth factor, interleukin-2, we conclude that activation of PKC is not essential for the growth-promoting action of interleukin-2.
Mills
G B
GB
Oncology Research Toronto General Hospital, Ontario, Canada.
Girard
P
P
Grinstein
S
S
Gelfand
E W
EW
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D004987:Ethers / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology*; D015759:Ionomycin; D007621:Karyotyping; D051379:Mice; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000172:deficiency* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D017923:Sodium-Hydrogen Exchangers; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology*
D002352:Carrier Proteins; D004987:Ethers; D007376:Interleukin-2; D010703:Phorbol Esters; D012333:RNA, Messenger; D017923:Sodium-Hydrogen Exchangers; D015759:Ionomycin; D011493:Protein Kinase C