Members of the protein kinase C (PKC) family of serine/threonine protein kinases have been implicated in numerous cellular responses in a large variety of cell types. The isoenzyme exhibits a relatively restricted pattern of expression with high protein levels found predominantly in hematopoietic cells and skeletal muscle. In addition, it is expressed in T, but not B lymphocytes, and is translocated from the cytosol to the membrane in a cell activation-dependent manner. In the present work we further analyzed whether subcellular localization and/or biological functions of involve physical interaction with other effector molecules. was found to interact with the 14-3-3τ protein, a known modulator of signaling effector molecules. Overexpression of 14-3-3τ resulted in the suppression of PKCθ-induced interleukin 2 promoter activation and inhibition of phorbol ester-induced cytosol to membrane translocation of PKCθ. In contrast, 14-3-3τ did not alter PKCθ enzymatic activity in vitro and did not undergo phosphorylation by PKCθ. In a different line of studies we have employed the yeast two hybrid system and identified a cDNA encoding a novel 335-amino acid PKCθ-interacting protein with a calculated mass of 37.5 kDa. This protein, termed PICOT, is expressed in various tissues, including in T cells, and displays an N-terminal thioredoxin-homology domain which is required for the interaction with PKC. Current studies are aimed at the characterization of the mode of interaction of PKCθ and either 14-3-3τ or PICOT, and the effects of the interaction on the subcellular localization and biological functions of theses three proteins.
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