Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.11.13 (
protein kinase C
)
49,245
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Murine macrophages respond to endotoxins by inducing a vast array of genes that play a major role in the host's response to infection and tumor growth. We have isolated and characterized a 1.8-kb cDNA, designated
IRG2
, from a cDNA library prepared from RNA isolated from the murine cell line, RAW 264.7, after bacterial LPS stimulation. The cDNA encodes a protein of 47 kDa that is the murine homologue of a small family of proteins described from IFN-induced human cells. The
IRG2
message does not appear until 3 h after LPS exposure and its induction is dependent on new protein synthesis.
IRG2
induction by LPS is slightly inhibited by the anti-inflammatory steroid, dexamethasone. Increasing cytosolic cAMP with either forskolin, dibutyryl cAMP, or 8-(4-chlorophenylthio)-cAMP caused marked inhibition of the LPS induction of
IRG2
. In contrast, activation of
PKC
with phorbol ester potentiated the LPS response. Removing extracellular Ca2+ with EGTA inhibited
IRG2
induction; increasing intracellular calcium with the calcium ionophore A23187 led to enhanced levels of the
IRG2
transcript. These data suggest that the induction of
IRG2
occurs via a
PKC
pathway.
...
PMID:Molecular cloning and characterization of a murine LPS-inducible cDNA. 820 6
A multitude of interferon (IFN)-inducible genes (IFIGs) are coordinately expressed in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE), emphasising the globle activating of signal pathway mediated by IFN-I in SLE. In this study, we investigated the mechanisms of expression regulation of
IFIT4
(interferon induced protein with tetratricopeptide repeats 4) by IFN-alpha. We found that IFN-alpha failed in inducing
IFIT4
in STAT1-negative U3A cells. Ectopic expression of STAT1, but not mutant STAT1-S727A, almost completely restored IFN-alpha2a-induced
IFIT4
expression. IFN-alpha induced the expression of
IFIT4
and STAT1 in THP-1 cells, and this process was significantly antagonized by the specific inhibitors of both
PKCdelta
and JNK or their dominant negative mutants respectively. The inhibition of JNK activity by its specific inhibitor or its dominant negative mutant suppressed both
IFIT4
expression and serine phosphorylation of STAT1 but not the activation of
PKCdelta
, while inhibition of
PKCdelta
suppressed activation of
IFIT4
, STAT1, and JNK. Our results suggest that the induction of
IFIT4
transcription by IFN-alpha depends upon sequential activation of
PKCdelta
, JNK and STAT1, and that the influence of
PKCdelta
or JNK on IFN-alpha-mediated induction of
IFIT4
is dependent upon the phosphorylation of STAT1 at Ser-727. The results in our experiment provide an in vitro model of the signaling mechanisms of IFIGs regulated by IFN-alpha, that is putatively thought to occur in vivo as the one of pathogenesis of SLE.
...
PMID:Sequential activation of protein kinase C delta and JNK is required for interferon-alpha-induced expression of IFIT4. 1793 93
