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Research Database PMU-SQQUID

GEF at work: Vav in protruding filopodia.
Kranewitter, WJ; Danninger, C; Gimona, M;
Cell Motil Cytoskeleton. 2001; 49(3): 154-160.
Originalarbeiten (Zeitschrift)

PMU-Authors

Gimona Mario

Abstract

The Dbl family proto-oncogene vav is a nucleotide exchange factor for Rho family GTPases and is involved in triggering cytoskeletal changes contributing to the alterations of cell shape and motility, as well as in the induction of gene expression. In vitro and in vivo Vav is regulated by multiple tyrosine phosphorylation and binding to phosphatidylinositol phosphates. Although recruitment of Vav to the plasma membrane appears important for the activation of Vav function, there is little information on the precise subcellular localization of Vav in living cells. Employing live video fluorescence and immunoelectron microscopy, we show that GFP-tagged full-length Vav, and several mutants in which the N-terminal regulatory calponin homology (CH) domain has been deleted, specifically localize to the tips of filopodia. This localization was congruent with a high content of tyrosine phosphorylation in these regions. Consistent with earlier observations, mutants lacking the C-terminal SH domain region were unable to translocate to the filopodia tips. The enrichment in filopodial tips persisted despite their lateral movement but was dependent on forward growth. Upon retraction, the signal was rapidly lost, indicating that Vav undergoes a specific and transient translocation in response to actin-based, protrusive (C) 2001 Wiley-Liss, Inc.


Useful keywords (using NLM MeSH Indexing)

Actins/metabolism*

Animals

Cell Movement/physiology

Cell Size/physiology

Cell Surface Extensions/physiology*

Cytoskeleton/metabolism

Cytoskeleton/ultrastructure

Gene Expression/physiology

Guanine Nucleotide Exchange Factors/metabolism*

Melanoma/metabolism

Mice

Microscopy, Fluorescence

Mutation/physiology

Oncogene Proteins/metabolism*

Phosphorylation

Proto-Oncogene Proteins c-vav

Pseudopodia/physiology*

Subcellular Fractions/metabolism

Tumor Cells, Cultured/metabolism


Find related publications in this database (Keywords)

vav
green fluorescent protein
filopodia
localization
dynamics