PKCtheta is required for the activation of human T lymphocytes induced by CD43 engagement.
The turnover of phosphoinositides leading to PKC activation constitutes one of the principal axes of intracellular signaling. In T lymphocytes, the enhanced and prolonged PKC activation resulting from the engagement of the TcR and co-receptor molecules ensures a productive T cell response. The CD43 co-receptor promotes activation and proliferation, by inducing IL-2 secretion and CD69 expression. CD43 engagement has been shown to promote phosphoinositide turnover and DAG production. Moreover, PKC activation was found to be required for the activation of the MAP kinase pathway in response to CD43 ligation. Here we show that CD43 engagement led to the membrane translocation and enzymatic activity of specific PKC isoenzymes: cPKC (alpha/beta), nPKC (epsilon and theta;), aPKC (zeta) and PKCmu. We also show that activation of PKCtheta; resulting from CD43 ligation induced CD69 expression through an ERK-dependent pathway leading to AP-1, NF-kappaB activation and an ERK independent pathway promoting NFAT activation. Together, these data suggest that PKCtheta; plays a critical role in the co-stimulatory functions of CD43 in human T cells.
del Rio
Roxana
R
Instituto de Biotecnología/Universidad Nacional Autónoma de México, AP 510-3 Cuernavaca, Mor. 62250, Mexico.
Rincón
Mercedes
M
Layseca-Espinosa
Esther
E
Fierro
Nora A
NA
Rosenstein
Yvonne
Y
Pedraza-Alva
Gustavo
G
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D037181:Lectins, C-Type; D051917:Leukosialin; D008213:Lymphocyte Activation; D020935:MAP Kinase Signaling System / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D021381:Protein Transport / Q000502:physiology; D012795:Sialoglycoproteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D004247:DNA; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D037181:Lectins, C-Type; D051917:Leukosialin; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; D012795:Sialoglycoproteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D000099192:CD69 Antigens; C465014:SPN protein, human; C076233:PRKCQ protein, human