Linked Life Data

17900104

Source:http://linkedlifedata.com/resource/pubmed/id/17900104

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2007-11-2
pubmed:abstractText
Cerebral cavernous malformations (CCM) are sporadic or inherited vascular lesions of the central nervous system characterized by dilated, thin-walled, leaky vessels. Linkage studies have mapped autosomal dominant mutations to three loci: ccm1 (KRIT1), ccm2 (OSM), and ccm3 (PDCD10). All three proteins appear to be scaffolds or adaptor proteins, as no enzymatic function can be attributed to them. Our previous results demonstrated that OSM is a scaffold for the assembly of the GTPase Rac and the MAPK kinase kinase MEKK3, for the hyperosmotic stress-dependent activation of p38 MAPK. Herein, we show that the three CCM proteins are members of a larger signaling complex. To define this complex, epitope-tagged wild type OSM or OSM harboring the mutation of F217-->A, which renders the OSM phosphotyrosine binding (PTB) domain unable to bind KRIT1, were stably introduced into RAW264.7 mouse macrophages. FLAG-OSM or FLAG-OSMF217A and the associated complex members were purified by immunoprecipitation using anti-FLAG antibody. OSM binding partners were identified by gel-based methods combined with electrospray ionization-MS or by multidimensional protein identification technology (MudPIT). Previously identified proteins that associate with OSM including KRIT1, MEKK3, Rac, and the KRIT1-binding protein ICAP-1 were found in the immunoprecipitates. In addition, we show for the first time that PDCD10 binds to OSM and is found in cellular CCM complexes. Other prominent proteins that bound the CCM complex include EF1A1, RIN2, and tubulin, with each interaction disrupted with the OSMF217A mutant protein. We further show that PDCD10 binds phosphatidylinositol di- and triphosphates and OSM binds phosphatidylinositol monophosphates. The findings define the targeting of the CCM complex to membranes and to proteins regulating trafficking and the cytoskeleton.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1535-3893
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4343-55
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:17900104-Animals, pubmed-meshheading:17900104-Apoptosis Regulatory Proteins, pubmed-meshheading:17900104-COS Cells, pubmed-meshheading:17900104-Cercopithecus aethiops, pubmed-meshheading:17900104-Cytoskeleton, pubmed-meshheading:17900104-Hemangioma, Cavernous, Central Nervous System, pubmed-meshheading:17900104-Humans, pubmed-meshheading:17900104-Immunoprecipitation, pubmed-meshheading:17900104-MAP Kinase Kinase Kinase 3, pubmed-meshheading:17900104-Membrane Proteins, pubmed-meshheading:17900104-Mice, pubmed-meshheading:17900104-Phosphates, pubmed-meshheading:17900104-Phosphatidylinositols, pubmed-meshheading:17900104-Protein Structure, Tertiary, pubmed-meshheading:17900104-Proteomics, pubmed-meshheading:17900104-Proto-Oncogene Proteins, pubmed-meshheading:17900104-Signal Transduction, pubmed-meshheading:17900104-Spectrometry, Mass, Electrospray Ionization, pubmed-meshheading:17900104-rac GTP-Binding Proteins
pubmed:year
2007
pubmed:articleTitle
Proteomic identification of the cerebral cavernous malformation signaling complex.
pubmed:affiliation
Department of Pharmacology and the Lineberger Comprehensive Cancer Center, School of Dentistry, University of North Carolina, Chapel Hill, CB #7365, Chapel Hill, North Carolina 27599-7365, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural