Linked Life Data

14676277

Source:http://linkedlifedata.com/resource/pubmed/id/14676277

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 2
pubmed:dateCreated
2003-12-16
pubmed:abstractText
Rac2 is a Rho GTPase that is expressed in cells of hematopoietic origin, including neutrophils and macrophages. We recently described an immunodeficient patient with severe, recurrent bacterial infections that had a point mutation in one allele of the Rac2 gene, resulting in the substitution of aspartate 57 with asparagine. To ascertain further the effects of Rac2D57N in leukocytes, Rac2D57N was expressed in primary murine bone-marrow-derived macrophages (cells that we show express approximately equal amounts of Rac1 and Rac2). Rac2D57N expression in macrophages inhibited membrane ruffling. Rac2D57N expression inhibited the formation of macropinosomes, demonstrating a functional effect of the loss of surface membrane dynamics. Surprisingly, Rac2D57N induced an elongated, spread morphology but did not affect microtubule networks. Rac2D57N also inhibited lipopolysaccharide-stimulated p38 kinase activation. Examination of guanine nucleotide binding to recombinant Rac2D57N revealed reduced dissociation of GDP and association of GTP. Coimmunoprecipitation studies of Rac2D57N with RhoGDI alpha and Tiam1 demonstrated increased binding of Rac2D57N to these upstream regulators of Rac signaling relative to the wild type. Enhanced binding of Rac2D57N to its upstream regulators would inhibit Rac-dependent effects on actin cytoskeletal dynamics and p38 kinase signaling.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9533
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
117
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
243-55
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:14676277-Actins, pubmed-meshheading:14676277-Animals, pubmed-meshheading:14676277-Bone Marrow, pubmed-meshheading:14676277-COS Cells, pubmed-meshheading:14676277-Cell Size, pubmed-meshheading:14676277-Cell Surface Extensions, pubmed-meshheading:14676277-Cercopithecus aethiops, pubmed-meshheading:14676277-Cytoskeleton, pubmed-meshheading:14676277-Enzyme Induction, pubmed-meshheading:14676277-Guanine Nucleotide Exchange Factors, pubmed-meshheading:14676277-Guanine Nucleotides, pubmed-meshheading:14676277-Macrophages, pubmed-meshheading:14676277-Mice, pubmed-meshheading:14676277-Microscopy, Fluorescence, pubmed-meshheading:14676277-Microtubules, pubmed-meshheading:14676277-Mitogen-Activated Protein Kinases, pubmed-meshheading:14676277-Mutation, pubmed-meshheading:14676277-Protein Binding, pubmed-meshheading:14676277-Proteins, pubmed-meshheading:14676277-p38 Mitogen-Activated Protein Kinases, pubmed-meshheading:14676277-rac GTP-Binding Proteins, pubmed-meshheading:14676277-rac1 GTP-Binding Protein
pubmed:year
2004
pubmed:articleTitle
Rac2D57N, a dominant inhibitory Rac2 mutant that inhibits p38 kinase signaling and prevents surface ruffling in bone-marrow-derived macrophages.
pubmed:affiliation
Department of Pharmacology, University of Colorado Health Sciences Center, 4200 East Ninth Ave, Denver, CO 80262, USA. amy_abdell@med.unc.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.