PMID- 10639334
OWN - NLM
STAT- MEDLINE
DCOM- 20000424
LR  - 20151119
IS  - 0021-9533 (Print)
IS  - 0021-9533 (Linking)
VI  - 113 ( Pt 3)
DP  - 2000 Feb
TI  - Endothelial cell retraction is induced by PAK2 monophosphorylation of myosin II.
PG  - 471-82
AB  - The p21-activated kinase (PAK) family includes several enzyme isoforms regulated 
      by the GTPases Rac1 and Cdc42. PAK1, found in brain, muscle and spleen, has been 
      implicated in triggering cytoskeletal rearrangements such as the dissolution of
      stress fibers and reorganization of focal complexes. The role of the more widely 
      distributed PAK2 in controlling the cytoskeleton has been less well studied.
      Previous work has demonstrated that PAK2 can monophosphorylate the myosin II
      regulatory light chain and induce retraction of permeabilized endothelial cells. 
      In this report we characterize PAK2's morphological and biochemical effect on
      intact endothelial cells utilizing microinjection of constitutively active PAK2. 
      Under these conditions we observed a modification of the actin cytoskeleton with 
      retraction of endothelial cell margins accompanied by an increase in
      monophosphorylation of myosin II. Selective inhibitors were used to analyze the
      mechanism of action of PAK2. Staurosporine, a direct inhibitor of PAK2, largely
      prevented the action of microinjected PAK2 in endothelial cells. Butanedione
      monoxime, a non-specific myosin ATPase inhibitor, also inhibited the effects of
      PAK2 implicating myosin in the changes in cytoskeletal reorganization. In
      contrast, KT5926, a specific inhibitor of myosin light chain kinase was
      ineffective in preventing the changes in morphology and the actin cytoskeleton.
      The additional finding that endogenous PAK2 associates with myosin II is
      consistent with the proposal that cell retraction and cytoskeletal rearrangements
      induced by microinjected PAK2 depend on the direct activation of myosin II by
      PAK2 monophosphorylation of the regulatory light chain.
FAU - Zeng, Q
AU  - Zeng Q
AD  - Department of Pathology, St Louis University School of Medicine St Louis,
      Missouri 63104-1028, USA.
FAU - Lagunoff, D
AU  - Lagunoff D
FAU - Masaracchia, R
AU  - Masaracchia R
FAU - Goeckeler, Z
AU  - Goeckeler Z
FAU - Cote, G
AU  - Cote G
FAU - Wysolmerski, R
AU  - Wysolmerski R
LA  - eng
GR  - AI-39690/AI/NIAID NIH HHS/United States
GR  - HL-45788/HL/NHLBI NIH HHS/United States
GR  - HL-61952/HL/NHLBI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Actins)
RN  - 0 (Alkaloids)
RN  - 0 (Carbazoles)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Indoles)
RN  - 0 (Myosin Light Chains)
RN  - 126643-38-7 (KT 5926)
RN  - 19SQ93LM6H (diacetylmonoxime)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (p21-Activated Kinases)
RN  - EC 2.7.11.18 (Myosin-Light-Chain Kinase)
RN  - EC 3.6.4.1 (Myosins)
RN  - H88EPA0A3N (Staurosporine)
RN  - K324J5K4HM (Diacetyl)
SB  - IM
MH  - Actins/metabolism
MH  - Alkaloids/pharmacology
MH  - Amino Acid Sequence
MH  - Animals
MH  - *Carbazoles
MH  - Cattle
MH  - Cell Line
MH  - Cell Size/drug effects
MH  - Cytoskeleton/*drug effects/ultrastructure
MH  - Diacetyl/analogs & derivatives/pharmacology
MH  - Endothelium, Vascular/cytology/*drug effects/metabolism
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/pharmacology
MH  - *Indoles
MH  - Microinjections
MH  - Molecular Sequence Data
MH  - Myosin Light Chains/*metabolism
MH  - Myosin-Light-Chain Kinase/antagonists & inhibitors
MH  - Myosins/*metabolism
MH  - Phosphorylation
MH  - Protein Processing, Post-Translational/*drug effects
MH  - Protein-Serine-Threonine Kinases/antagonists & inhibitors/*metabolism
MH  - Rabbits
MH  - Staurosporine/pharmacology
MH  - p21-Activated Kinases
EDAT- 2000/01/20 09:00
MHDA- 2000/04/29 09:00
CRDT- 2000/01/20 09:00
PHST- 2000/01/20 09:00 [pubmed]
PHST- 2000/04/29 09:00 [medline]
PHST- 2000/01/20 09:00 [entrez]
PST - ppublish
SO  - J Cell Sci. 2000 Feb;113 ( Pt 3):471-82.