Protein kinase C delta specifically associates with phosphatidylinositol 3-kinase following cytokine stimulation.
Phosphatidylinositol (PI) 3-kinase is activated as a result of cytokine-induced association of the enzyme with specific tyrosine-phosphorylated proteins. PI 3-kinase lipid products, PI 3, 4-P2 and PI 3,4,5-P3, have been shown, in vitro, to directly activate novel and atypical protein kinase C (PKC) isozymes. However, the mechanism by which PI 3-kinase may be involved in regulation of PKC isoforms in vivo is presently unknown. We investigated a possible relationship by looking for associations between these enzymes. We found that in a human erythroleukemia cell line, as well as in rabbit platelets, PI 3-kinase and PKCdelta associate in a specific manner that is modulated by cell activation. Granulocyte-macrophage colony-stimulating factor treatment of cells caused increased association of PKCdelta and PI 3-kinase as did treatment of platelets with platelet-activating factor. Results using two PI 3-kinase inhibitors, wortmannin and LY-294002, showed that the former inhibited this association, while the latter did not, suggesting that PI 3-kinase lipid products may not be a prerequisite for the PI 3-kinase/PKCdelta association. Our results also suggest that tyrosine phosphorylation of PKCdelta is not involved in its association with PI 3-kinase.
Ettinger
S L
SL
Department of Medicine, Jack Bell Research Centre, University of British Columbia, Vancouver, British Columbia V6H 3Z6, Canada.
Lauener
R W
RW
Duronio
V
V
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000201:enzymology*; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015848:Interleukin-5 / Q000494:pharmacology; D007527:Isoenzymes / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D015471:Leukemia, Basophilic, Acute; D004915:Leukemia, Erythroblastic, Acute; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D019000:Phosphotyrosine / Q000032:analysis; D010972:Platelet Activating Factor / Q000494:pharmacology; D011485:Protein Binding; D011493:Protein Kinase C / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D051745:Protein Kinase C-delta; D011817:Rabbits; D051381:Rats; D017455:Receptors, IgE / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D000077191:Wortmannin
D000730:Androstadienes; D002867:Chromones; D016207:Cytokines; D004791:Enzyme Inhibitors; D007377:Interleukin-3; D015848:Interleukin-5; D007527:Isoenzymes; D009025:Morpholines; D010972:Platelet Activating Factor; D017455:Receptors, IgE; D011994:Recombinant Proteins; D019000:Phosphotyrosine; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); C497260:Prkcd protein, rat; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D000077191:Wortmannin