Linked Life Data

17609419

Source:http://linkedlifedata.com/resource/pubmed/id/17609419

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-9-19
pubmed:abstractText
The rgsRhoGEFs comprise a subfamily of three guanine nucleotide exchange factors, which function in linking heterotrimeric G-proteins to the monomeric RhoGTPase. Here, we reveal the novel finding that oligomerization of leukemia-associated RhoGEF (LARG) functions to prevent nucleocytoplasmic shuttling and to retain LARG in the cytoplasm. We establish that oligomerization is mediated by a predicted coiled-coil sequence (amino acids 1507-1520) in the extreme C terminus of LARG and that substitution of isoleucines 1507/1510 with alanines disrupts homo-oligomerization and leads to nucleocytoplasmic shuttling via the CRM1 nuclear transport pathway. In addition, we demonstrate that induced dimerization of an otherwise nuclear monomeric LARG mutant promotes cytoplasmic localization. Furthermore, we establish that nuclear import of monomeric LARG is mediated by the nuclear localization sequence (29)PTDKKQK(35) in the extreme N terminus. We propose that nucleocytoplasmic shuttling provides a mechanism for spatially regulating the activity of LARG toward its cytoplasmic targets and potentially new nuclear targets.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
72
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
993-1002
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Disruption of oligomerization induces nucleocytoplasmic shuttling of leukemia-associated rho Guanine-nucleotide exchange factor.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, Thomas Jefferson University, 233 S. 10 Street, 839 BLSB, Philadelphia, PA 19107, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural