PMID- 10330143
OWN - NLM
STAT- MEDLINE
DCOM- 19990617
LR  - 20190508
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 6
DP  - 1999 Jun
TI  - Targeting of p38 mitogen-activated protein kinases to MEF2 transcription factors.
PG  - 4028-38
AB  - Mitogen-activated protein (MAP) kinase-mediated signalling to the nucleus is an
      important event in the conversion of extracellular signals into a cellular
      response. However, the existence of multiple MAP kinases which phosphorylate
      similar phosphoacceptor motifs poses a problem in maintaining substrate
      specificity and hence the correct biological response. Both the extracellular
      signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) subfamilies of 
      MAP kinases use a second specificity determinant and require docking to their
      transcription factor substrates to achieve maximal substrate activation. In this 
      study, we demonstrate that among the different MAP kinases, the MADS-box
      transcription factors MEF2A and MEF2C are preferentially phosphorylated and
      activated by the p38 subfamily members p38alpha and p38beta2. The efficiency of
      phosphorylation in vitro and transcriptional activation in vivo of MEF2A and
      MEF2C by these p38 subtypes requires the presence of a kinase docking domain
      (D-domain). Furthermore, the D-domain from MEF2A is sufficient to confer p38
      responsiveness on different transcription factors, and reciprocal effects are
      observed upon the introduction of alternative D-domains into MEF2A. These results
      therefore contribute to our understanding of signalling to MEF2 transcription
      factors and demonstrate that the requirement for substrate binding by MAP kinases
      is an important facet of three different subclasses of MAP kinases (ERK, JNK, and
      p38).
FAU - Yang, S H
AU  - Yang SH
AD  - Department of Biochemistry and Genetics, The Medical School, University of
      Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, United Kingdom.
FAU - Galanis, A
AU  - Galanis A
FAU - Sharrocks, A D
AU  - Sharrocks AD
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (MADS Domain Proteins)
RN  - 0 (MEF2 Transcription Factors)
RN  - 0 (MEF2A protein, human)
RN  - 0 (MEF2C protein, human)
RN  - 0 (Myogenic Regulatory Factors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (ets-Domain Protein Elk-1)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent 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  - Animals
MH  - Blotting, Western
MH  - COS Cells
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*genetics/metabolism
MH  - DNA-Binding Proteins/*genetics
MH  - Escherichia coli/genetics
MH  - Genes, Reporter
MH  - Genes, jun/physiology
MH  - HeLa Cells
MH  - Humans
MH  - Luciferases/metabolism
MH  - MADS Domain Proteins
MH  - MEF2 Transcription Factors
MH  - *Mitogen-Activated Protein Kinases
MH  - Models, Genetic
MH  - Myogenic Regulatory Factors
MH  - Phosphorylation
MH  - Plasmids
MH  - Protein Binding
MH  - Protein Kinases/metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Recombinant Fusion Proteins
MH  - Sequence Homology, Amino Acid
MH  - Time Factors
MH  - Transcription Factors/*genetics
MH  - ets-Domain Protein Elk-1
MH  - p38 Mitogen-Activated Protein Kinases
PMC - PMC104362
EDAT- 1999/05/18 00:00
MHDA- 1999/05/18 00:01
CRDT- 1999/05/18 00:00
PHST- 1999/05/18 00:00 [pubmed]
PHST- 1999/05/18 00:01 [medline]
PHST- 1999/05/18 00:00 [entrez]
AID - 10.1128/mcb.19.6.4028 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 Jun;19(6):4028-38. doi: 10.1128/mcb.19.6.4028.