Studies with transfected and permeabilized RBL-2H3 cells reveal unique inhibitory properties of protein kinase C gamma.
To characterize protein kinase C (PKC) gamma, an isozyme found exclusively in brain and spinal cord, its cDNA was introduced into basophilic RBL-2H3 cells that lack this isozyme. The expression of PKC gamma significantly attenuated antigen-induced responses including hydrolysis of inositol phospholipids, increase in cytosolic calcium, and secretion of granules but enhanced antigen-induced release of arachidonic acid. Instead of a sustained increase in cytosolic calcium, antigen now induced calcium oscillations; possibly as a consequence of suppression of the phospholipase C activity and incomplete emptying of internal calcium stores. In addition, PKC gamma appeared to inhibit activation of other PKC isozymes because phorbol 12-myristate 13-acetate failed to act synergistically with the Ca(2+)-ionophore on secretion. This was confirmed in other studies where PKC gamma was shown to suppress the transduction of stimulatory signals by other isozymes of PKC on provision of these isozymes to PKC-depleted permeabilized cells. The studies in total indicated that only PKC gamma was capable of inhibiting both early and distal signals for secretion including those signals transduced by endogenous isozymes of PKC.
Baumgartner
R A
RA
Laboratory of Chemical Pharmacology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
Ozawa
K
K
Cunha-Melo
J R
JR
Yamada
K
K
Gusovsky
F
F
Beaven
M A
MA
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002463:Cell Membrane Permeability; D018076:DNA, Complementary; D004140:Dinitrophenols / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D006868:Hydrolysis / Q000187:drug effects; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D008979:Moloney murine leukemia virus / Q000235:genetics; D010716:Phosphatidylinositols / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D064546:Protein Kinase C beta; D051745:Protein Kinase C-delta; D051381:Rats; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D018076:DNA, Complementary; D004140:Dinitrophenols; D007527:Isoenzymes; D010716:Phosphatidylinositols; C034638:dinitrophenyl-bovine serum albumin; D012710:Serum Albumin, Bovine; D016718:Arachidonic Acid; C497260:Prkcd protein, rat; C087857:protein kinase C gamma; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051745:Protein Kinase C-delta; D001619:beta-N-Acetylhexosaminidases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium