PMID- 10496324
OWN - NLM
STAT- MEDLINE
DCOM- 19991004
LR  - 20190516
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 66
IP  - 3
DP  - 1999 Sep
TI  - Localization of p21-activated kinase 1 (PAK1) to pseudopodia, membrane ruffles,
      and phagocytic cups in activated human neutrophils.
PG  - 521-7
AB  - Leukocyte chemoattractants are known to stimulate signaling pathways that involve
      Rho family GTPases. Direct evidence for the regulation of the leukocyte
      cytoskeleton by Rho GTPases and their effector targets is limited. The
      p21-activated kinases (PAKs) are specific targets of activated GTP-bound Rac and 
      Cdc42, and have been proposed as regulators of chemoattractant-driven actin
      cytoskeletal changes in fibroblasts. PAK1 colocalizes with F-actin to cortical
      actin structures in stimulated fibroblasts, and activated PAK1 mutants induce
      membrane ruffling and polarized cytoskeletal rearrangements. We investigated
      whether PAK1 was associated with remodeling of the actin cytoskeleton in
      activated human neutrophils. We monitored the redistribution of PAK1 and F-actin 
      into the actin cytoskeleton after stimulation of human neutrophils with the
      chemoattractant N-formyl-methionyl-leucyl-phenylalanine (fMLP) or the particulate
      stimulus, opsonized zymosan (OZ). PAK1 exhibited a similar distribution as
      F-actin in fMLP-stimulated leukocytes, localizing in membrane ruffles and to
      lamellipodia at the leading edge of polarized cells. Addition of OZ induced
      phagocytic uptake of this particulate stimulus, and PAK1 re-localized to the
      F-actin-rich pseudopodia and phagocytic cups associated with this process. Once
      the OZ was internalized, there was little PAK1 localized around the ingested
      particles, suggesting that PAK1 may be regulating the cytoskeletal extensions and
      events required for engulfment of bacteria, but not the subsequent steps of
      internalization. Localization of PAK1 and F-actin in cytoskeletal structures was 
      abolished by the actin polymerization inhibitor cytochalasin D and the
      phosphatidylinositol 3-kinase inhibitor wortmannin. Our data suggest that PAK1
      may regulate a subset of cytoskeletal dynamics initiated by chemoattractant and
      phagocytic stimuli in human neutrophils.
FAU - Dharmawardhane, S
AU  - Dharmawardhane S
AD  - Department of Immunology, The Scripps Research Institute, La Jolla, California
      92037, USA.
FAU - Brownson, D
AU  - Brownson D
FAU - Lennartz, M
AU  - Lennartz M
FAU - Bokoch, G M
AU  - Bokoch GM
LA  - eng
GR  - GM39434/GM/NIGMS NIH HHS/United States
GR  - GM44428/GM/NIGMS NIH HHS/United States
GR  - GM45983/GM/NIGMS NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Actins)
RN  - 0 (Androstadienes)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Opsonin Proteins)
RN  - 22144-77-0 (Cytochalasin D)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 80295-43-8 (Complement C3b)
RN  - 9010-72-4 (Zymosan)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-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 3.6.1.- (GTP-Binding Proteins)
RN  - EC 3.6.5.2 (cdc42 GTP-Binding Protein)
RN  - EC 3.6.5.2 (rac GTP-Binding Proteins)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - Actins/ultrastructure
MH  - Adult
MH  - Androstadienes/pharmacology
MH  - Cell Cycle Proteins/physiology
MH  - Cell Polarity
MH  - *Chemotaxis, Leukocyte/drug effects
MH  - Complement C3b/physiology
MH  - Cytochalasin D/pharmacology
MH  - Cytoskeleton/*chemistry/drug effects/ultrastructure
MH  - Enzyme Inhibitors/pharmacology
MH  - GTP-Binding Proteins/physiology
MH  - Humans
MH  - Microscopy, Confocal
MH  - Microscopy, Fluorescence
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Neutrophils/drug effects/*enzymology/ultrastructure
MH  - Opsonin Proteins/pharmacology
MH  - *Phagocytosis/drug effects
MH  - Phosphatidylinositol 3-Kinases/antagonists & inhibitors/physiology
MH  - Protein-Serine-Threonine Kinases/*analysis/physiology
MH  - Pseudopodia/*enzymology
MH  - Wortmannin
MH  - Zymosan/pharmacology
MH  - cdc42 GTP-Binding Protein
MH  - p21-Activated Kinases
MH  - rac GTP-Binding Proteins
EDAT- 1999/09/25 00:00
MHDA- 1999/09/25 00:01
CRDT- 1999/09/25 00:00
PHST- 1999/09/25 00:00 [pubmed]
PHST- 1999/09/25 00:01 [medline]
PHST- 1999/09/25 00:00 [entrez]
AID - 10.1002/jlb.66.3.521 [doi]
PST - ppublish
SO  - J Leukoc Biol. 1999 Sep;66(3):521-7. doi: 10.1002/jlb.66.3.521.