TY - JOUR
T1 - Inhibition of the c-Jun N-terminal kinase/AP-1 and NF-κB pathways by PICOT, a novel protein kinase C-interacting protein with a thioredoxin homology domain
AU - Witte, Stephan
AU - Villalba, Martin
AU - Bi, Kun
AU - Liu, Yuhong
AU - Isakov, Noah
AU - Altman, Amnon
PY - 2000/1/21
Y1 - 2000/1/21
N2 - Protein kinase C-θ (PKCθ) is a Ca2+-independent PKC isoform that is selectively expressed in T lymphocytes (and muscle), and is thought to play an important role in T cell receptor-induced activation. To gain a better understanding of the function and regulation of PKCθ, we have employed the yeast two-hybrid system to identify PKCθ-interacting proteins. We report the isolation and characterization of a cDNA encoding a novel 335-amino acid (37.5-kDa) PKCθ-interacting protein termed PICOT (for PKC-interacting cousin of thioredoxin). PICOT is expressed in various tissues, including in T cells, where it colocalizes with PKCθ. PICOT displays an N-terminal thioredoxin homology domain, which is required for the interaction with PKC. Comparison of the unique C-terminal region of PICOT with expressed sequence tag data bases revealed two tandem repeats of a novel domain that is highly conserved from plants to mammals. Transient overexpression of full-length PICOT (but not its N- or C-terminal fragments) in T cells inhibited the activation of c- Jun N-terminal kinase (but not extracellular signal-regulated kinase), and the transcription factors AP-1 or NF-κB. These findings suggest that PICOT and its evolutionary conserved homologues may interact with PKC-related kinases in multiple organisms and, second, that it plays a role in regulating the function of the thioredoxin system.
AB - Protein kinase C-θ (PKCθ) is a Ca2+-independent PKC isoform that is selectively expressed in T lymphocytes (and muscle), and is thought to play an important role in T cell receptor-induced activation. To gain a better understanding of the function and regulation of PKCθ, we have employed the yeast two-hybrid system to identify PKCθ-interacting proteins. We report the isolation and characterization of a cDNA encoding a novel 335-amino acid (37.5-kDa) PKCθ-interacting protein termed PICOT (for PKC-interacting cousin of thioredoxin). PICOT is expressed in various tissues, including in T cells, where it colocalizes with PKCθ. PICOT displays an N-terminal thioredoxin homology domain, which is required for the interaction with PKC. Comparison of the unique C-terminal region of PICOT with expressed sequence tag data bases revealed two tandem repeats of a novel domain that is highly conserved from plants to mammals. Transient overexpression of full-length PICOT (but not its N- or C-terminal fragments) in T cells inhibited the activation of c- Jun N-terminal kinase (but not extracellular signal-regulated kinase), and the transcription factors AP-1 or NF-κB. These findings suggest that PICOT and its evolutionary conserved homologues may interact with PKC-related kinases in multiple organisms and, second, that it plays a role in regulating the function of the thioredoxin system.
UR - http://www.scopus.com/inward/record.url?scp=0034695550&partnerID=8YFLogxK
U2 - 10.1074/jbc.275.3.1902
DO - 10.1074/jbc.275.3.1902
M3 - Article
C2 - 10636891
AN - SCOPUS:0034695550
SN - 0021-9258
VL - 275
SP - 1902
EP - 1909
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 3
ER -