PMID- 15870290
OWN - NLM
STAT- MEDLINE
DCOM- 20050614
LR  - 20181113
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 25
IP  - 10
DP  - 2005 May
TI  - Vav activation and function as a rac guanine nucleotide exchange factor in 
      macrophage colony-stimulating factor-induced macrophage chemotaxis.
PG  - 4211-20
AB  - Signal transduction mediated by phosphatidylinositol 3-kinase (PI 3-kinase) is 
      regulated by hydrolysis of its products, a function performed by the 145-kDa SH2 
      domain-containing inositol phosphatase (SHIP). Here, we show that bone marrow 
      macrophages of SHIP(-/-) animals have elevated levels of phosphatidylinositol 
      3,4,5-trisphosphate [PI (3,4,5)P(3)] and displayed higher and more prolonged 
      chemotactic responses to macrophage colony-stimulating factor (M-CSF) and 
      elevated levels of F-actin relative to wild-type macrophages. We also found that 
      the small GTPase Rac was constitutively active and its upstream activator Vav was 
      constitutively phosphorylated in SHIP(-/-) macrophages. Furthermore, we show that 
      Vav in wild-type macrophages is recruited to the membrane in a PI 
      3-kinase-dependent manner through the Vav pleckstrin homology domain upon M-CSF 
      stimulation. Dominant inhibitory mutants of both Rac and Vav blocked chemotaxis. 
      We conclude that Vav acts as a PI 3-kinase-dependent activator for Rac activation 
      in macrophages stimulated with M-CSF and that SHIP regulates macrophage 
      M-CSF-triggered chemotaxis by hydrolysis of PI (3,4,5)P(3).
FAU - Vedham, Vidya
AU  - Vedham V
AD  - The Oklahoma Medical Research Foundation, Immunobiology and Cancer Program, 825 
      N.E. 13th St., Oklahoma City, OK 73104, USA.
FAU - Phee, Hyewon
AU  - Phee H
FAU - Coggeshall, K Mark
AU  - Coggeshall KM
LA  - eng
GR  - R01 AI049264/AI/NIAID NIH HHS/United States
GR  - R01 CA064268/CA/NCI NIH HHS/United States
GR  - AI49264/AI/NIAID NIH HHS/United States
GR  - CA64268/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Phosphatidylinositol Phosphates)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-vav)
RN  - 0 (Vav1 protein, mouse)
RN  - 0 (phosphatidylinositol 3,4,5-triphosphate)
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
RN  - EC 3.1.3.86 (INPPL1 protein, human)
RN  - EC 3.1.3.86 (Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases)
RN  - EC 3.6.5.2 (rac GTP-Binding Proteins)
SB  - IM
MH  - Animals
MH  - Cell Cycle Proteins/chemistry/*metabolism
MH  - Cell Membrane/metabolism
MH  - Cells, Cultured
MH  - Chemotaxis/*drug effects
MH  - Enzyme Activation
MH  - Macrophage Colony-Stimulating Factor/*pharmacology
MH  - Macrophages/cytology/*drug effects/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphatidylinositol Phosphates/metabolism
MH  - Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
MH  - Phosphoric Monoester Hydrolases/deficiency/metabolism
MH  - Protein Structure, Tertiary
MH  - Protein Transport
MH  - Proto-Oncogene Proteins/chemistry/*metabolism
MH  - Proto-Oncogene Proteins c-vav
MH  - Signal Transduction/drug effects
MH  - rac GTP-Binding Proteins/chemistry/*metabolism
PMC - PMC1087731
EDAT- 2005/05/05 09:00
MHDA- 2005/06/15 09:00
PMCR- 2005/05/01
CRDT- 2005/05/05 09:00
PHST- 2005/05/05 09:00 [pubmed]
PHST- 2005/06/15 09:00 [medline]
PHST- 2005/05/05 09:00 [entrez]
PHST- 2005/05/01 00:00 [pmc-release]
AID - 25/10/4211 [pii]
AID - 2135-04 [pii]
AID - 10.1128/MCB.25.10.4211-4220.2005 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2005 May;25(10):4211-20. doi: 10.1128/MCB.25.10.4211-4220.2005.