PMID- 8538746
OWN - NLM
STAT- MEDLINE
DCOM- 19960208
LR  - 20131121
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 379
IP  - 6560
DP  - 1996 Jan 4
TI  - Defective thymocyte proliferation and IL-2 production in transgenic mice 
      expressing a dominant-negative form of CREB.
PG  - 81-5
AB  - The basic/leucine zipper (bZip) transcription factor, CREB, binds to the CRE 
      element (TGANNTCA). The transcriptional activity of CREB requires phosphorylation 
      of the protein on a serine residue at position 119 (ref. 6). CREs are present in 
      a number of T-cell genes but the precise role of CREB in T-cell differentiation 
      and function was unknown. Here we show that resting thymocytes contain 
      predominantly unphosphorylated (inactive) CREB, which is rapidly activated by 
      phosphorylation on Ser 119 following thymocyte activation. T-cell development is 
      normal in transgenic mice that express a dominant-negative form of CREB 
      (CREBA119, with alanine at position 119) under the control of the T-cell-specific 
      CD2 promoter/enhancer. In contrast, thymocytes and T cells from these animals 
      display a profound proliferative defect characterized by markedly decreased 
      interleukin-2 production, G1 cell-cycle arrest and subsequent apoptotic death in 
      response to a number of different activation signals. This proliferative defect 
      is associated with the markedly reduced induction of c-jun, c-fos, Fra-2 and FosB 
      following activation of the CREBA119 transgenic thymocytes. We propose that 
      T-cell activation leads to the phosphorylation and activation of CREB, which in 
      turn is required for normal induction of the transcription factor AP1 and 
      subsequent interleukin-2 production and cell-cycle progression.
FAU - Barton, K
AU  - Barton K
AD  - Department of Medicine, University of Chicago, Illinois 60637, USA.
FAU - Muthusamy, N
AU  - Muthusamy N
FAU - Chanyangam, M
AU  - Chanyangam M
FAU - Fischer, C
AU  - Fischer C
FAU - Clendenin, C
AU  - Clendenin C
FAU - Leiden, J M
AU  - Leiden JM
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Activating Transcription Factors)
RN  - 0 (Blood Proteins)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Interleukin-2)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Transcription Factors)
RN  - 452VLY9402 (Serine)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Activating Transcription Factors
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Blood Proteins/metabolism
MH  - Cell Differentiation/physiology
MH  - Cell Division
MH  - Cyclic AMP Response Element-Binding Protein/chemistry/genetics/*physiology
MH  - DNA/metabolism
MH  - G1 Phase
MH  - Interleukin-2/*biosynthesis
MH  - Lymphocyte Activation
MH  - Mice
MH  - Mice, Transgenic
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Phosphorylation
MH  - Receptors, Antigen, T-Cell/metabolism
MH  - Regulatory Sequences, Nucleic Acid
MH  - Serine/metabolism
MH  - T-Lymphocytes/*cytology/immunology
MH  - Thymus Gland/*cytology
MH  - Transcription Factors/metabolism
EDAT- 1996/01/04 00:00
MHDA- 1996/01/04 00:01
CRDT- 1996/01/04 00:00
PHST- 1996/01/04 00:00 [pubmed]
PHST- 1996/01/04 00:01 [medline]
PHST- 1996/01/04 00:00 [entrez]
AID - 10.1038/379081a0 [doi]
PST - ppublish
SO  - Nature. 1996 Jan 4;379(6560):81-5. doi: 10.1038/379081a0.