PMID- 10559936
OWN - NLM
STAT- MEDLINE
DCOM- 19991206
LR  - 20091119
IS  - 1465-7392 (Print)
IS  - 1465-7392 (Linking)
VI  - 1
IP  - 5
DP  - 1999 Sep
TI  - Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin
      cytoskeletal dynamics.
PG  - 253-9
AB  - Extracellular signals regulate actin dynamics through small GTPases of the
      Rho/Rac/Cdc42 (p21) family. Here we show that p21-activated kinase (Pak1)
      phosphorylates LIM-kinase at threonine residue 508 within LIM-kinase's activation
      loop, and increases LIM-kinase-mediated phosphorylation of the actin-regulatory
      protein cofilin tenfold in vitro. In vivo, activated Rac or Cdc42 increases
      association of Pak1 with LIM-kinase; this association requires structural
      determinants in both the amino-terminal regulatory and the carboxy-terminal
      catalytic domains of Pak1. A catalytically inactive LIM-kinase interferes with
      Rac-, Cdc42- and Pak1-dependent cytoskeletal changes. A Pak1-specific inhibitor, 
      corresponding to the Pak1 autoinhibitory domain, blocks LIM-kinase-induced
      cytoskeletal changes. Activated GTPases can thus regulate actin depolymerization 
      through Pak1 and LIM-kinase.
FAU - Edwards, D C
AU  - Edwards DC
AD  - Department of Chemistry, University of California at San Diego, La Jolla
      92093-0650, USA.
FAU - Sanders, L C
AU  - Sanders LC
FAU - Bokoch, G M
AU  - Bokoch GM
FAU - Gill, G N
AU  - Gill GN
LA  - eng
GR  - CA58689/CA/NCI NIH HHS/United States
GR  - DK13149/DK/NIDDK NIH HHS/United States
GR  - GM39434/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nat Cell Biol
JT  - Nature cell biology
JID - 100890575
RN  - 0 (Actins)
RN  - 0 (Recombinant Proteins)
RN  - 1114-81-4 (Phosphothreonine)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (LIMK1 protein, human)
RN  - EC 2.7.11.1 (Lim Kinases)
RN  - EC 2.7.11.1 (PAK1 protein, human)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (p21-Activated Kinases)
RN  - EC 3.6.5.2 (cdc42 GTP-Binding Protein)
RN  - EC 3.6.5.2 (rac GTP-Binding Proteins)
SB  - IM
CIN - Nat Cell Biol. 1999 Sep;1(5):E115-7. PMID: 10559948
MH  - Actins/*physiology
MH  - Animals
MH  - COS Cells
MH  - Cell Line
MH  - Cell Membrane/physiology/ultrastructure
MH  - Cytoskeleton/*physiology
MH  - Enzyme Activation
MH  - Humans
MH  - Kinetics
MH  - Lim Kinases
MH  - Mutagenesis, Site-Directed
MH  - Phosphorylation
MH  - Phosphothreonine/metabolism
MH  - Protein Kinases/*metabolism
MH  - Protein-Serine-Threonine Kinases/*metabolism
MH  - Recombinant Proteins/metabolism
MH  - Sequence Deletion
MH  - Signal Transduction
MH  - Transfection
MH  - Zinc Fingers
MH  - cdc42 GTP-Binding Protein/*metabolism
MH  - p21-Activated Kinases
MH  - rac GTP-Binding Proteins/*metabolism
EDAT- 1999/11/13 09:00
MHDA- 2001/03/23 10:01
CRDT- 1999/11/13 09:00
PHST- 1999/11/13 09:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/11/13 09:00 [entrez]
AID - 10.1038/12963 [doi]
PST - ppublish
SO  - Nat Cell Biol. 1999 Sep;1(5):253-9. doi: 10.1038/12963.