PMID- 10652349
OWN - NLM
STAT- MEDLINE
DCOM- 20000302
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 5
DP  - 2000 Feb 4
TI  - Identification of amino acid residues and protein kinases involved in the
      regulation of NFATc subcellular localization.
PG  - 3543-51
AB  - The subcellular localization of the transcription factor NFATc is tightly
      regulated by the calcium-regulated phosphatase calcineurin, which acts to
      directly dephosphorylate NFATc, causing its rapid translocation from the
      cytoplasm to the nucleus. The calcineurin-mediated nuclear localization of NFATc 
      is opposed by poorly defined protein kinases that act either to directly
      antagonize nuclear import or, alternatively, to promote nuclear export. Here, we 
      provide evidence that the cellular protein kinases JNK, ERK, p38, and CK2
      (formerly casein kinase II) are involved in the regulation of NFATc subcellular
      localization. We show that JNK, ERK, and p38 physically associate with the NFATc 
      N-terminal regulatory domain and can directly phosphorylate functionally
      important residues involved in regulating NFATc subcellular localization, namely 
      Ser(172) and the conserved NFATc Ser-Pro repeats. Moreover, we found that
      overexpression of JNK, ERK, or p38 is able to block ionomycin-induced NFATc
      nuclear translocation, whereas treatment of cells with both PD98059 and SB202190,
      which inhibit MAPK/SAPK signaling pathways, is sufficient to trigger NFATc
      nuclear localization. Finally, we show that CK2 also binds the N terminus of
      NFATc and phosphorylates functionally important amino acid residues, including a 
      conserved amino acid motif located downstream of each of the NFATc Ser-Pro
      repeats that appears to be important for regulating NFATc nuclear export.
      Collectively, these studies identify functionally important amino acid residues
      and protein kinases involved in the regulation of NFATc subcellular localization.
FAU - Porter, C M
AU  - Porter CM
AD  - Department of Microbiology, Northwestern University Medical School, Chicago,
      Illinois 60611, USA.
FAU - Havens, M A
AU  - Havens MA
FAU - Clipstone, N A
AU  - Clipstone NA
LA  - eng
GR  - GM55292/GM/NIGMS 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 (DNA-Binding Proteins)
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.- (Protein Kinases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Biological Transport
MH  - COS Cells
MH  - DNA-Binding Proteins/*metabolism
MH  - Humans
MH  - Jurkat Cells
MH  - Lymphocyte Activation
MH  - Molecular Sequence Data
MH  - NFATC Transcription Factors
MH  - Nuclear Proteins/metabolism
MH  - Phosphoproteins/metabolism
MH  - Protein Kinases/*metabolism
MH  - Signal Transduction
MH  - T-Lymphocytes/*metabolism
MH  - Transcription Factors/*metabolism
EDAT- 2000/02/01 09:00
MHDA- 2000/03/04 09:00
CRDT- 2000/02/01 09:00
PHST- 2000/02/01 09:00 [pubmed]
PHST- 2000/03/04 09:00 [medline]
PHST- 2000/02/01 09:00 [entrez]
AID - 10.1074/jbc.275.5.3543 [doi]
AID - S0021-9258(18)30938-4 [pii]
PST - ppublish
SO  - J Biol Chem. 2000 Feb 4;275(5):3543-51. doi: 10.1074/jbc.275.5.3543.