PMID- 10581204
OWN - NLM
STAT- MEDLINE
DCOM- 20000106
LR  - 20211203
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 266
IP  - 1
DP  - 1999 Dec 9
TI  - Identification of two distinct regions of p38 MAPK required for substrate binding 
      and phosphorylation.
PG  - 284-9
AB  - The mechanism by which different mitogen activated protein kinases (MAPKs) 
      distinguish between different substrates is poorly understood. For example, p38 
      and SAPK4 are two closely related p38 MAPKs that both phosphorylate ATF2 and MBP. 
      However, p38 phosphorylates MAPKAPK-2 and -3, whereas SAPK4 does not. In this 
      study, we have used mutagenesis to determine the regions of p38 required for 
      substrate selection. Alanine scanning mutagenesis identified one region of p38 
      that was required for its ability to phosphorylate MAPKAPK-2 and -3, but that did 
      not significantly affect its binding to these substrates. Chimeras of p38 and 
      SAPK4 identified a second region of p38 that affected the ability of p38 to both 
      bind and phosphorylate MAPKAPK-2 and -3. Hence, we show for the first time that 
      MAPKs contain two distinct regions for recognizing and phosphorylating protein 
      substrates.
CI  - Copyright 1999 Academic Press.
FAU - Gum, R J
AU  - Gum RJ
AD  - Department of Molecular Biology, SmithKline Beecham Pharmaceuticals, King of 
      Prussia, PA19406, USA.
FAU - Young, P R
AU  - Young PR
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (ATF2 protein, human)
RN  - 0 (Activating Transcription Factor 2)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Myelin Basic Protein)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.1.- (MAP-kinase-activated kinase 2)
RN  - EC 2.7.1.- (MAP-kinase-activated kinase 3)
RN  - EC 2.7.1.- (Mitogen-Activated Protein Kinase 13)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - OF5P57N2ZX (Alanine)
SB  - IM
MH  - Activating Transcription Factor 2
MH  - Alanine/genetics
MH  - Amino Acid Sequence
MH  - Binding Sites
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Mitogen-Activated Protein Kinase 13
MH  - Mitogen-Activated Protein Kinases/*chemistry/genetics/*metabolism
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Mutagenesis/genetics
MH  - Mutation/genetics
MH  - Myelin Basic Protein/metabolism
MH  - Phosphorylation
MH  - Precipitin Tests
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Recombinant Fusion Proteins/chemistry/genetics/metabolism
MH  - Structure-Activity Relationship
MH  - Substrate Specificity
MH  - Transcription Factors/metabolism
MH  - Transfection
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 1999/12/03 00:00
MHDA- 1999/12/03 00:01
CRDT- 1999/12/03 00:00
PHST- 1999/12/03 00:00 [pubmed]
PHST- 1999/12/03 00:01 [medline]
PHST- 1999/12/03 00:00 [entrez]
AID - S0006-291X(99)91787-4 [pii]
AID - 10.1006/bbrc.1999.1787 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 1999 Dec 9;266(1):284-9. doi: 10.1006/bbrc.1999.1787.