Linked Life Data

15723800

Source:http://linkedlifedata.com/resource/pubmed/id/15723800

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-2-22
pubmed:abstractText
CDM (CED-5, Dock180, Myoblast city) family members have been recently identified as novel, evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases . They regulate multiple processes, including embryonic development, cell migration, apoptotic-cell engulfment, tumor invasion, and HIV-1 infection, in diverse model systems . However, the mechanism(s) of regulation of CDM proteins has not been well understood. Here, our studies on the prototype member Dock180 reveal a steric-inhibition model for regulating the Dock180 family of GEFs. At basal state, the N-terminal SH3 domain of Dock180 binds to the distant catalytic Docker domain and negatively regulates the function of Dock180. Further studies revealed that the SH3:Docker interaction sterically blocks Rac access to the Docker domain. Interestingly, ELMO binding to the SH3 domain of Dock180 disrupted the SH3:Docker interaction, facilitated Rac access to the Docker domain, and contributed to the GEF activity of the Dock180/ELMO complex. Additional genetic rescue studies in C. elegans suggested that the regulation of the Docker-domain-mediated GEF activity by the SH3 domain and its adjoining region is evolutionarily conserved. This steric-inhibition model may be a general mechanism for regulating multiple SH3-domain-containing Dock180 family members and may have implications for a variety of biological processes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0960-9822
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
371-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15723800-Adaptor Proteins, Signal Transducing, pubmed-meshheading:15723800-Amino Acid Sequence, pubmed-meshheading:15723800-Animals, pubmed-meshheading:15723800-Blotting, Western, pubmed-meshheading:15723800-Caenorhabditis elegans, pubmed-meshheading:15723800-Cells, Cultured, pubmed-meshheading:15723800-Guanine Nucleotide Exchange Factors, pubmed-meshheading:15723800-Humans, pubmed-meshheading:15723800-Immunoprecipitation, pubmed-meshheading:15723800-Models, Biological, pubmed-meshheading:15723800-Molecular Sequence Data, pubmed-meshheading:15723800-Protein Binding, pubmed-meshheading:15723800-Protein Structure, Tertiary, pubmed-meshheading:15723800-Sequence Alignment, pubmed-meshheading:15723800-rac GTP-Binding Proteins, pubmed-meshheading:15723800-rho GTP-Binding Proteins, pubmed-meshheading:15723800-src Homology Domains
pubmed:year
2005
pubmed:articleTitle
A Steric-inhibition model for regulation of nucleotide exchange via the Dock180 family of GEFs.
pubmed:affiliation
Beirne Carter Center for Immunology Research, Department of Microbiology, University of Virginia, Charlottesville, VA 22908 USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't