Linked Life Data

15302586

Source:http://linkedlifedata.com/resource/pubmed/id/15302586

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-8-10
pubmed:abstractText
The c-fes locus encodes a cytoplasmic protein-tyrosine kinase (Fes) previously shown to accelerate nerve growth factor (NGF)-induced neurite outgrowth in rat PC12 cells. Here, we investigated the role of the Rho family small GTPases Rac1 and Cdc42 in Fes-mediated neuritogenesis, which have been implicated in neuronal differentiation in other systems. Fes-induced acceleration of neurite outgrowth in response to NGF treatment was completely blocked by the expression of dominant-negative Rac1 or Cdc42. Expression of a kinase-active mutant of Fes induced constitutive relocalization of endogenous Rac1 to the cell periphery in the absence of NGF, and led to dramatic actin reorganization and spontaneous neurite extension. We also investigated the breakpoint cluster region protein (Bcr), which possesses the Dbl and PH domains characteristic of guanine nucleotide exchange factors for Rho family GTPases, as a possible link between Fes, Rac/Cdc42 activation, and neuritogenesis. Coexpression of a GFP-Bcr fusion protein containing the Fes binding and tyrosine phosphorylation sites (amino acids 162-413) completely suppressed neurite outgrowth triggered by Fes. Conversely, coexpression of full-length Bcr with wild-type Fes in PC12 cells induced NGF-independent neurite formation. Taken together, these data suggest that Fes and Bcr cooperate to activate Rho family GTPases as part of a novel pathway regulating neurite extension in PC12 cells, and provide more evidence for an emerging role for Fes in neuronal differentiation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0014-4827
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
299
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
188-98
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15302586-Animals, pubmed-meshheading:15302586-Binding Sites, pubmed-meshheading:15302586-Cell Differentiation, pubmed-meshheading:15302586-Growth Cones, pubmed-meshheading:15302586-Humans, pubmed-meshheading:15302586-Mutation, pubmed-meshheading:15302586-Nerve Growth Factor, pubmed-meshheading:15302586-Neurites, pubmed-meshheading:15302586-PC12 Cells, pubmed-meshheading:15302586-Phosphorylation, pubmed-meshheading:15302586-Protein Structure, Tertiary, pubmed-meshheading:15302586-Protein Transport, pubmed-meshheading:15302586-Protein-Tyrosine Kinases, pubmed-meshheading:15302586-Proto-Oncogene Proteins, pubmed-meshheading:15302586-Proto-Oncogene Proteins c-bcr, pubmed-meshheading:15302586-Proto-Oncogene Proteins c-fes, pubmed-meshheading:15302586-Rats, pubmed-meshheading:15302586-Recombinant Fusion Proteins, pubmed-meshheading:15302586-cdc42 GTP-Binding Protein, pubmed-meshheading:15302586-rac1 GTP-Binding Protein
pubmed:year
2004
pubmed:articleTitle
The c-Fes tyrosine kinase cooperates with the breakpoint cluster region protein (Bcr) to induce neurite extension in a Rac- and Cdc42-dependent manner.
pubmed:affiliation
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't