PICOT, protein kinase C theta-interacting protein, is a novel regulator of FcepsilonRI-mediated mast cell activation.
PICOT (PKC-interacting cousin of thioredoxin) consists of one thioredoxin homology domain in the N-terminal and two tandem PICOT homology domains in the C-terminal. PICOT specifically interacts with protein kinase C theta (PKC-theta) via its thioredoxin homology domain and acts as an important modulator of T cell receptor (TCR)-signaling. Using PICOT overexpressing rat basophilic leukemia cells (RBL-2H3), we evaluated the effect of PICOT overexpression on the FcepsilonRI-mediated signaling. In comparison to the control cells, introduction of PICOT to RBL-2H3 cells induced increased degranulation and the activation of NFAT and in the expression of IL-4 and TNF-alpha transcripts by FcepsilonRI-crosslinking, whereas no significant change was observed with the elevation of ERK1/2 and p38 MAP kinase phosphorylation and NF-kappaB activation by FcepsilonRI aggregation. More interesting was the exogenous PICOT overexpression in RBL-2H3 cells causing a large decrease in the elevation of JNK phosphorylation. PICOT-regulated FcepsilonRI-mediated signals in RBL-2H3 cells and acted as a positive regulator on IL-4 and TNF-alpha expression, NFAT and degranulation signal pathways and a negative regulator on a JNK signal pathway. Considering that PICOT has no enzymatic activity, the regulation of PICOT on FcepsilonRI-signaling may depend on PICOT-associated molecule(s).
Kato
Natsumi
N
Department of Life Science, Rikkyo (St. Paul's) University, 3-34-1, Nishi-ikebukuro, Toshima-ku, Tokyo 171-8501, Japan.
Motohashi
Satoru
S
Okada
Takuya
T
Ozawa
Tomoko
T
Mashima
Keisuke
K
D000276:Adjuvants, Immunologic / Q000378:metabolism*; D000818:Animals; D001491:Basophils / Q000187:drug effects / Q000276:immunology*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D015550:Cell Degranulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011490:Protein Disulfide Reductase (Glutathione); D051381:Rats; D017455:Receptors, IgE / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D000276:Adjuvants, Immunologic; D002352:Carrier Proteins; D016207:Cytokines; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D017455:Receptors, IgE; D011490:Protein Disulfide Reductase (Glutathione); C498606:Txnl2 protein, mouse; D020928:Mitogen-Activated Protein Kinases