PICOT, protein kinase C theta-interacting protein, is a novel regulator of FcepsilonRI-mediated mast cell activation.

Abstract:

: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).

journal_name

Cell Immunol

journal_title

Cellular immunology

authors

Kato N,Motohashi S,Okada T,Ozawa T,Mashima K

doi

10.1016/j.cellimm.2008.04.005

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

62-7

issue

1

eissn

0008-8749

issn

1090-2163

pii

S0008-8749(08)00075-0

journal_volume

251

pub_type

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