PMID- 15302577
OWN - NLM
STAT- MEDLINE
DCOM- 20040930
LR  - 20211203
IS  - 0014-4827 (Print)
IS  - 0014-4827 (Linking)
VI  - 299
IP  - 1
DP  - 2004 Sep 10
TI  - Mitogen-activated 3p kinase is active in the nucleus.
PG  - 101-9
AB  - The MAPK-activated kinase 3pK (chromosome 3p kinase), also known as MAPKAPK-3, is 
      a member of a family of kinases that are activated by more than one 
      mitogen-activated protein kinase (MAPK). 3pK is unique since it was shown to be 
      activated by three members of the MAPK family, namely 
      extracellular-signal-regulated kinase (ERK), p38, and Jun-N-terminal kinase 
      (JNK). Accordingly, 3pK is highly activated both by mitogens and by 
      stress-inducing agents or proinflammatory cytokines. Studies utilizing dominant 
      interfering mutants and pharmacological agents revealed that upon mitogenic 
      stimulation, 3pK is exclusively activated via the classical MAPK cascade, while 
      stress-induced activation of 3pK is mainly mediated by p38. The mechanism 
      defining the specificity of kinase action in response to mitogenic versus stress 
      activation remains unknown. Here we show that 3pK is transported to the cytoplasm 
      upon both stress and mitogenic stimulation. While kinetics of nuclear export are 
      similar in both situations, the activation pattern differs substantially. In the 
      mitogenic situation, active 3pK remains in the nucleus for a significant time and 
      there may fulfill mitogen-specific functions. These data not only show that 
      nuclear export of the kinase is mechanistically uncoupled from its activation, 
      but also provide a novel mechanism by which cells may modulate enzyme activity 
      toward a stimulus-specific response.
FAU - Zakowski, Vera
AU  - Zakowski V
AD  - Institut fur Molekulare Medizin (IMM), Heinrich-Heine-Universitat Dusseldorf, 
      D-40225 Dusseldorf, Germany.
FAU - Keramas, Georgios
AU  - Keramas G
FAU - Kilian, Karin
AU  - Kilian K
FAU - Rapp, Ulf R
AU  - Rapp UR
FAU - Ludwig, Stephan
AU  - Ludwig S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Mitogens)
RN  - EC 2.7.1.- (MAP-kinase-activated kinase 3)
RN  - EC 2.7.11.1 (Protein Serine-Threonine 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)
SB  - IM
MH  - Active Transport, Cell Nucleus/drug effects/genetics
MH  - Cell Line
MH  - Cell Nucleus/drug effects/*enzymology/genetics
MH  - Cytoplasm/enzymology
MH  - Enzyme Activation/physiology
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - JNK Mitogen-Activated Protein Kinases
MH  - MAP Kinase Signaling System/drug effects/genetics
MH  - Mitogen-Activated Protein Kinases/drug effects/metabolism
MH  - Mitogens/*pharmacology
MH  - Mutation/drug effects/genetics
MH  - Protein Serine-Threonine Kinases/drug effects/genetics/*metabolism
MH  - Stress, Physiological/genetics/metabolism
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 2004/08/11 05:00
MHDA- 2004/10/02 05:00
CRDT- 2004/08/11 05:00
PHST- 2004/01/22 00:00 [received]
PHST- 2004/05/20 00:00 [revised]
PHST- 2004/08/11 05:00 [pubmed]
PHST- 2004/10/02 05:00 [medline]
PHST- 2004/08/11 05:00 [entrez]
AID - S0014482704002988 [pii]
AID - 10.1016/j.yexcr.2004.05.027 [doi]
PST - ppublish
SO  - Exp Cell Res. 2004 Sep 10;299(1):101-9. doi: 10.1016/j.yexcr.2004.05.027.