12-Deoxyphorbol-13-O-phenylacetate 20 acetate [an agonist of protein kinase C beta 1 (PKC beta 1)] induces DNA synthesis, interleukin-2 (IL-2) production, IL-2 receptor alpha-chain (CD25) and beta-chain (CD122) expression, and translocation of PKC beta isozyme in human peripheral blood lymphocytes: evidence for a role of PKC beta 1 in human T cell activation.
To determine a role of protein kinase C (PKC) isozymes in lymphocyte activation, human peripheral blood mononuclear cells were activated with 12-deoxyphorbol-13-O-phenylacetate (dPP; an agonist of both calcium-dependent and calcium-independent PKC isozymes), thymeleatoxin (TX; an activator of calcium-dependent PKC alpha, beta, and gamma), and 12-deoxyphorbol-13-O-phenylacetate 20 acetate (dPPA; an activator of PKC beta 1 isozyme) and examined for DNA synthesis, lymphocyte proliferation, interleukin-2 (IL-2) production, expression of IL-2 receptor alpha and beta chains on CD3+, CD4+, and CD8+ T lymphocytes and CD20+ B lymphocytes, and translocation of PKC beta isozyme from cytosol to membrane fraction. The results show that dPPA activates lymphocytes by inducing the above changes in a manner analogous to that of dPP, TX, and phorbol myristate acetate. These data suggest that PKC beta 1 is involved in the activation of human peripheral blood T and B lymphocytes.
Aggarwal
S
S
Division of Basic and Clinical Immunology, University of California, Irvine 92717.
Lee
S
S
Mathur
A
A
Gollapudi
S
S
Gupta
S
S
D004247:DNA / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis; D007527:Isoenzymes / Q000819:agonists / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000819:agonists / Q000097:blood / Q000502:physiology*; D064546:Protein Kinase C beta; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology
D007376:Interleukin-2; D007527:Isoenzymes; D010703:Phorbol Esters; D015375:Receptors, Interleukin-2; C029705:12-deoxyphorbolphenylacetate-20-acetate; D004247:DNA; D011493:Protein Kinase C; D064546:Protein Kinase C beta