TY - JOUR
T1 - Mitogen-induced human T cell proliferation is associated with increased expression of selected PKC genes
AU - Isakov, Noah
AU - Mally, Martin I.
AU - Altman, Amnon
N1 - Funding Information:
*The work reported herein was supported, in part, by grants from the National Institutes of Health (CA35299), Gemini Science, Inc., The U.S.A.-Israel Binational Science Foun-dation, the Israel Academy of Sciences and Humanities, the Chief Scientist of the Israeli Ministry of Health, the Israel Cancer Association, and an ICRF Career Development Award (N.I.).
PY - 1992/1/1
Y1 - 1992/1/1
N2 - The induction of T cell proliferation and differentiation into mature effector cells is dependent on two principal exogenous signals that are provided by the antigen or mitogen and IL2. The enzyme protein kinase C (PKC) has a major role in the antigen-receptor signalling pathway in T cells, but appears not to be involved in signalling via the IL2-receptor (IL2-R). Since both pathways trigger a series of sequentially coordinated transcriptional events in which numerous genes are activated, we tested whether a T cell mitogen acting via the TCR/CD3 complex, and IL2, affect the expression of the conventional, Ca2+-dependent, PKC genes (α, β and γ) in T cells. Stimulation of human peripheral blood lymphocytes or an enriched population of human T cells with phytohemagglutinin resulted in augmented mRNA levels of PKCα and PKCβ, but not PKCγ-gene. The response peaked at 24-48 hr when a 3-5-fold increase was observed. Stimulation of IL2-Rα-expressing T cells with human recombinant IL2 induced cell proliferation and transcription of the IL2-Rα gene (> 100-fold), but did not change mRNA levels of PKCa or PKCβ genes. The results suggest that stimulation of human T cells with mitogens acting via the TCR/CD3 complex, that involve activation of PKC, is accompanied also by a late activation of selected PKC genes. By contrast, agonists such as IL2, that operate via a different signalling pathway, do not modify the expression of any of the known conventional PKC genes.
AB - The induction of T cell proliferation and differentiation into mature effector cells is dependent on two principal exogenous signals that are provided by the antigen or mitogen and IL2. The enzyme protein kinase C (PKC) has a major role in the antigen-receptor signalling pathway in T cells, but appears not to be involved in signalling via the IL2-receptor (IL2-R). Since both pathways trigger a series of sequentially coordinated transcriptional events in which numerous genes are activated, we tested whether a T cell mitogen acting via the TCR/CD3 complex, and IL2, affect the expression of the conventional, Ca2+-dependent, PKC genes (α, β and γ) in T cells. Stimulation of human peripheral blood lymphocytes or an enriched population of human T cells with phytohemagglutinin resulted in augmented mRNA levels of PKCα and PKCβ, but not PKCγ-gene. The response peaked at 24-48 hr when a 3-5-fold increase was observed. Stimulation of IL2-Rα-expressing T cells with human recombinant IL2 induced cell proliferation and transcription of the IL2-Rα gene (> 100-fold), but did not change mRNA levels of PKCa or PKCβ genes. The results suggest that stimulation of human T cells with mitogens acting via the TCR/CD3 complex, that involve activation of PKC, is accompanied also by a late activation of selected PKC genes. By contrast, agonists such as IL2, that operate via a different signalling pathway, do not modify the expression of any of the known conventional PKC genes.
UR - http://www.scopus.com/inward/record.url?scp=0026650879&partnerID=8YFLogxK
U2 - 10.1016/0161-5890(92)90131-G
DO - 10.1016/0161-5890(92)90131-G
M3 - Article
AN - SCOPUS:0026650879
SN - 0161-5890
VL - 29
SP - 927
EP - 933
JO - Molecular Immunology
JF - Molecular Immunology
IS - 7-8
ER -
