Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2000-3-31
pubmed:abstractText
The Dbl oncogene is a putative exchange factor for the small GTPases RhoA and Cdc42, which are involved in actin polymerization into stress fibers and filopodia, respectively. We report here that, upon adhesion to fibronectin, Dbl-transformed NIH3T3 cells display a contracted, polygonal shape with a high number of short stress fibers. In contrast, untransformed NIH3T3 cells acquire the characteristic fibroblast morphology and organize a regular mesh of long stress fibers. We show that in Dbl-transformed and in untransformed NIH3T3 cells the different shape and actin cytoskeleton organization observed in the early steps of adhesion involves activation of distinct GTPases. Upon adhesion to fibronectin, cell morphology of Dbl-transformed NIH3T3 cells depends on activation of RhoA and not of Cdc42. In contrast Cdc42 activation is necessary to untransfected NIH3T3 cells to acquire their fibroblast shape. In both Dbl-transformed and in untransformed NIH3T3 cells a basal Rac activation is necessary to support stress fiber organization, while constitutive Rac activation promotes ruffles and lamellipodia formation. As a consequence of RhoA activation, Dbl-transformed cells show high activity of ROCK-alpha and CRIK kinases, two known RhoA effectors. In addition Dbl-transformed and NIH3T3 cells expressing the constitutive active form of RhoA are less motile on fibronectin than cells expressing constitutive active Cdc42. We conclude that in NIH3T3 cells in response to fibronectin the expression of the Dbl oncogene leads to a predominant activation of RhoA which both supports the peculiar cell shape and actin cytoskeleton organization in stress fibers and regulates cell motility.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1428-36
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:10723134-3T3 Cells, pubmed-meshheading:10723134-Actins, pubmed-meshheading:10723134-Animals, pubmed-meshheading:10723134-COS Cells, pubmed-meshheading:10723134-Cell Line, Transformed, pubmed-meshheading:10723134-Cell Migration Inhibition, pubmed-meshheading:10723134-Cell Movement, pubmed-meshheading:10723134-Cell Size, pubmed-meshheading:10723134-Cell Transformation, Neoplastic, pubmed-meshheading:10723134-Cytoskeleton, pubmed-meshheading:10723134-Enzyme Activation, pubmed-meshheading:10723134-Fibronectins, pubmed-meshheading:10723134-Gene Expression Regulation, pubmed-meshheading:10723134-Guanine Nucleotide Exchange Factors, pubmed-meshheading:10723134-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:10723134-Mice, pubmed-meshheading:10723134-Protein-Serine-Threonine Kinases, pubmed-meshheading:10723134-Retroviridae Proteins, Oncogenic, pubmed-meshheading:10723134-cdc42 GTP-Binding Protein, pubmed-meshheading:10723134-rhoA GTP-Binding Protein
pubmed:year
2000
pubmed:articleTitle
Distinct involvement of cdc42 and RhoA GTPases in actin organization and cell shape in untransformed and Dbl oncogene transformed NIH3T3 cells.
pubmed:affiliation
Dipartimento di Genetica, Biologia e Biochimica, Università di Torino, Via Santena 5bis, 10126, Torino, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't