PMID- 19542442
OWN - NLM
STAT- MEDLINE
DCOM- 20090820
LR  - 20090622
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 183
IP  - 1
DP  - 2009 Jul 1
TI  - Vav1 regulates the migration and adhesion of dendritic cells.
PG  - 310-8
LID - 10.4049/jimmunol.0802096 [doi]
AB  - Dendritic cells (DCs) are the most potent APCs for activating naive T cells, a 
      process facilitated by the ability of immature DCs to mature and home to lymph 
      nodes after encountering an inflammatory stimulus. Proteins involved in 
      cytoskeletal rearrangement play an important role in regulating the adherence and 
      motility of DCs. Vav1, a guanine nucleotide exchange factor for Rho family 
      GTPases, mediates cytoskeletal rearrangement in hematopoietic cells following 
      integrin ligation. We show that Vav1 is not required for the normal maturation of 
      DCs in vitro; however, it is critical for DC binding to fibronectin and regulates 
      the distribution but not the formation of podosomes. We also found that DC Vav1 
      was an important component of a signaling pathway involving focal adhesion 
      kinase, phospholipase C-gamma2, and ERK1/2 following integrin ligation. 
      Surprisingly, Vav1(-/-) DCs had increased rates of migration in vivo compared 
      with wild-type control DCs. In vitro findings show that the presence of adhesive 
      substrates such as fibronectin resulted in inhibition of migration. However, 
      there was less inhibition in the absence of Vav1. These findings suggest that DC 
      migration is negatively regulated by adhesion and integrin-mediated signaling and 
      that Vav1 has a central role in this process.
FAU - Spurrell, David R
AU  - Spurrell DR
AD  - Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.
FAU - Luckashenak, Nancy A
AU  - Luckashenak NA
FAU - Minney, Derek C
AU  - Minney DC
FAU - Chaplin, Anna
AU  - Chaplin A
FAU - Penninger, Joseph M
AU  - Penninger JM
FAU - Liwski, Robert S
AU  - Liwski RS
FAU - Clements, James L
AU  - Clements JL
FAU - West, Kenneth A
AU  - West KA
LA  - eng
GR  - AI54666/AI/NIAID NIH HHS/United States
GR  - CA16056/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Fibronectins)
RN  - 0 (Integrins)
RN  - 0 (Ligands)
RN  - 0 (Proto-Oncogene Proteins c-vav)
RN  - 0 (Vav1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Cell Adhesion/genetics/immunology
MH  - Cell Differentiation/genetics/immunology
MH  - Cell Movement/genetics/*immunology
MH  - Cells, Cultured
MH  - Dendritic Cells/*cytology/*immunology/metabolism
MH  - Fibronectins/metabolism
MH  - Integrins/metabolism
MH  - Ligands
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Protein Binding/genetics/immunology
MH  - Proto-Oncogene Proteins c-vav/biosynthesis/deficiency/genetics/*physiology
MH  - Pseudopodia/genetics/immunology/metabolism
MH  - Signal Transduction/genetics/immunology
EDAT- 2009/06/23 09:00
MHDA- 2009/08/21 09:00
CRDT- 2009/06/23 09:00
PHST- 2009/06/23 09:00 [entrez]
PHST- 2009/06/23 09:00 [pubmed]
PHST- 2009/08/21 09:00 [medline]
AID - 183/1/310 [pii]
AID - 10.4049/jimmunol.0802096 [doi]
PST - ppublish
SO  - J Immunol. 2009 Jul 1;183(1):310-8. doi: 10.4049/jimmunol.0802096.