PMID- 10196227
OWN - NLM
STAT- MEDLINE
DCOM- 19990517
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 16
DP  - 1999 Apr 16
TI  - Structural features of LIM kinase that control effects on the actin cytoskeleton.
PG  - 11352-61
AB  - LIM kinase phosphorylates and inactivates the actin binding/depolymerizing factor
      cofilin and induces actin cytoskeletal changes. Several unique structural
      features within LIM kinase were investigated for their roles in regulation of LIM
      kinase activity. Disruption of the second LIM domain or the PDZ domain or
      deletion of the entire amino terminus increased activity in vivo measured as
      increasing aggregation of the actin cytoskeleton. A kinase-deleted alternate
      splice product was identified and characterized. This alternate splice product
      and a kinase inactive mutant inhibited LIM kinase in vivo, indicating that the
      amino terminus suppresses activity of the kinase domain. Mutation of threonine
      508 in the activation loop to valine abolished activity whereas replacement with 
      2 glutamic acid residues resulted in a fully active enzyme. Dephosphorylation of 
      LIM kinase inhibited cofilin phosphorylation. Mutation of the basic insert in the
      activation loop inhibited activity in vivo, but not in vitro. These results
      indicate phosphorylation is an essential regulatory feature of LIM kinase and
      indicate that threonine 508 and the adjacent basic insert sequences of the
      activation loop are required for this process. A combination of structural
      features are thus involved in receiving upstream signals that regulate LIM
      kinase-induced actin cytoskeletal reorganization.
FAU - Edwards, D C
AU  - Edwards DC
AD  - Department of Chemistry, University of California San Diego, School of Medicine, 
      La Jolla, California 92093, USA.
FAU - Gill, G N
AU  - Gill GN
LA  - eng
SI  - GENBANK/AF134379
GR  - DK13149/DK/NIDDK NIH HHS/United States
PT  - Journal Article
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 (Actin Depolymerizing Factors)
RN  - 0 (Actins)
RN  - 0 (DNA Primers)
RN  - 0 (Microfilament Proteins)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (LIMK1 protein, human)
RN  - EC 2.7.11.1 (Lim Kinases)
SB  - IM
MH  - Actin Depolymerizing Factors
MH  - Actins/*metabolism
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - COS Cells
MH  - Catalysis
MH  - Cell Line
MH  - Cytoskeleton/*metabolism
MH  - DNA Primers
MH  - Humans
MH  - Lim Kinases
MH  - Microfilament Proteins/metabolism
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Phosphorylation
MH  - Protein Kinases/chemistry/genetics/*metabolism
MH  - RNA Splicing
MH  - Substrate Specificity
EDAT- 1999/04/10 00:00
MHDA- 1999/04/10 00:01
CRDT- 1999/04/10 00:00
PHST- 1999/04/10 00:00 [pubmed]
PHST- 1999/04/10 00:01 [medline]
PHST- 1999/04/10 00:00 [entrez]
AID - 10.1074/jbc.274.16.11352 [doi]
AID - S0021-9258(19)73646-1 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Apr 16;274(16):11352-61. doi: 10.1074/jbc.274.16.11352.