PMID- 10636891
OWN - NLM
STAT- MEDLINE
DCOM- 20000224
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 3
DP  - 2000 Jan 21
TI  - Inhibition of the c-Jun N-terminal kinase/AP-1 and NF-kappaB pathways by PICOT, a
      novel protein kinase C-interacting protein with a thioredoxin homology domain.
PG  - 1902-9
AB  - Protein kinase C-theta (PKCtheta) is a Ca(2+)-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 PKCtheta, we have employed the
      yeast two-hybrid system to identify PKCtheta-interacting proteins. We report the 
      isolation and characterization of a cDNA encoding a novel 335-amino acid (37.
      5-kDa) PKCtheta-interacting protein termed PICOT (for PKC-interacting cousin of
      thioredoxin). PICOT is expressed in various tissues, including in T cells, where 
      it colocalizes with PKCtheta. 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-kappaB. 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.
FAU - Witte, S
AU  - Witte S
AD  - Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San
      Diego, California 92121, USA.
FAU - Villalba, M
AU  - Villalba M
FAU - Bi, K
AU  - Bi K
FAU - Liu, Y
AU  - Liu Y
FAU - Isakov, N
AU  - Isakov N
FAU - Altman, A
AU  - Altman A
LA  - eng
GR  - CA35299/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Carrier Proteins)
RN  - 0 (GLRX3 protein, human)
RN  - 0 (NF-kappa B)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Transcription Factor AP-1)
RN  - 52500-60-4 (Thioredoxins)
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Carrier Proteins/*chemistry/pharmacology/*physiology
MH  - Glutathione Transferase/metabolism
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Jurkat Cells
MH  - Lymphocyte Activation/physiology
MH  - MAP Kinase Signaling System/drug effects
MH  - Mitogen-Activated Protein Kinases/*antagonists & inhibitors
MH  - Molecular Sequence Data
MH  - NF-kappa B/*antagonists & inhibitors
MH  - Plasmids
MH  - Protein Binding
MH  - Protein Kinase C/*metabolism
MH  - Recombinant Fusion Proteins/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sequence Homology, Amino Acid
MH  - T-Lymphocytes/drug effects
MH  - Thioredoxins/*metabolism
MH  - Transcription Factor AP-1/*antagonists & inhibitors
MH  - Transfection
MH  - Two-Hybrid System Techniques
EDAT- 2000/01/15 09:00
MHDA- 2000/02/26 09:00
CRDT- 2000/01/15 09:00
PHST- 2000/01/15 09:00 [pubmed]
PHST- 2000/02/26 09:00 [medline]
PHST- 2000/01/15 09:00 [entrez]
AID - 10.1074/jbc.275.3.1902 [doi]
PST - ppublish
SO  - J Biol Chem. 2000 Jan 21;275(3):1902-9. doi: 10.1074/jbc.275.3.1902.