PMID- 10518804
OWN - NLM
STAT- MEDLINE
DCOM- 19991214
LR  - 20190620
IS  - 0014-2956 (Print)
IS  - 0014-2956 (Linking)
VI  - 265
IP  - 3
DP  - 1999 Nov
TI  - Ca2+-induced p38/SAPK signalling inhibited by the immunosuppressant cyclosporin A
      in human peripheral blood mononuclear cells.
PG  - 1075-84
AB  - To understand the effects of the immunosuppressant cyclosporin A (CsA) on
      Ca2+-mediated intracellular signalling pathways in human peripheral blood
      mononuclear cells (PBMCs), we investigated its effects on the activity profiles
      of mitogen-activated protein kinase (MAPK) cascades. PBMCs, or subpopulations
      thereof, were simultaneously stimulated with a phorbol ester and the calcium
      ionophore ionomycin, in the presence or absence of therapeutic concentrations of 
      CsA. In these primary human cells, CsA significantly inhibited
      PMA/ionomycin-mediated and ionomycin-mediated activation of the MAPK kinase MKK6,
      as well as its downstream kinases SAPK2a (p38alpha) and MAPKAP-K2. PMA/ionomycin 
      treatment also mediated activation of SAPK1 (JNKs) which was inhibited by CsA.
      Treatment with ionomycin alone also resulted in CsA-sensitive activation of
      SAPK1. With regard to transcription factors targeted by the Ca2+-induced MAPK
      signalling network, we found CsA to inhibit the ionomycin-mediated
      phosphorylation of ATF2 at Thr71. We identified the heterodimeric transcription
      factor ATF2/CREB as constitutively binding to the essential cAMP response element
      (CRE) site within the Ca2+-regulated DNA polymerase beta promoter and
      contributing to the activation of this promoter. Our data implicate ATF2
      phosphorylation status as a nuclear sensor within PBMCs that monitors converging 
      intracellular Ca2+-signalling pathways.
FAU - Kreideweiss, S
AU  - Kreideweiss S
AD  - Medizinische Hochschule Hannover, Institut fur Molekularbiologie, Hannover,
      Germany.
FAU - Ahlers, C
AU  - Ahlers C
FAU - Nordheim, A
AU  - Nordheim A
FAU - Ruhlmann, A
AU  - Ruhlmann A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Biochem
JT  - European journal of biochemistry
JID - 0107600
RN  - 0 (ATF2 protein, human)
RN  - 0 (Activating Transcription Factor 2)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Transcription Factors)
RN  - 56092-81-0 (Ionomycin)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.1.- (MAP-kinase-activated kinase 2)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 6)
RN  - EC 2.7.12.2 (MAP2K6 protein, human)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - EC 3.1.3.16 (Calcineurin)
SB  - IM
MH  - Activating Transcription Factor 2
MH  - Base Sequence
MH  - Binding Sites
MH  - Calcineurin/metabolism
MH  - Calcium Signaling/*drug effects
MH  - *Calcium-Calmodulin-Dependent Protein Kinases
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Cyclosporine/*pharmacology
MH  - DNA/genetics
MH  - Enzyme Activation/drug effects
MH  - Genes, pol/drug effects
MH  - Humans
MH  - Immunosuppressive Agents/*pharmacology
MH  - In Vitro Techniques
MH  - Intracellular Signaling Peptides and Proteins
MH  - Ionomycin/pharmacology
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Leukocytes, Mononuclear/*drug effects/enzymology/*metabolism
MH  - MAP Kinase Kinase 6
MH  - Mitogen-Activated Protein Kinase Kinases/metabolism
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Phosphorylation
MH  - Promoter Regions, Genetic
MH  - Protein-Serine-Threonine Kinases/metabolism
MH  - Transcription Factors/metabolism
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 1999/10/16 00:00
MHDA- 1999/10/16 00:01
CRDT- 1999/10/16 00:00
PHST- 1999/10/16 00:00 [pubmed]
PHST- 1999/10/16 00:01 [medline]
PHST- 1999/10/16 00:00 [entrez]
AID - ejb830 [pii]
AID - 10.1046/j.1432-1327.1999.00830.x [doi]
PST - ppublish
SO  - Eur J Biochem. 1999 Nov;265(3):1075-84. doi: 10.1046/j.1432-1327.1999.00830.x.