Linked Life Data

11395506

Source:http://linkedlifedata.com/resource/pubmed/id/11395506

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
32
pubmed:dateCreated
2001-8-6
pubmed:abstractText
Phospholipase Cepsilon (PLCepsilon) is a novel class of phosphoinositide-specific PLC characterized by possession of CDC25 homology and Ras/Rap1-associating domains. We and others have shown that human PLCepsilon is translocated from the cytoplasm to the plasma membrane and activated by direct association with Ras at its Ras/Rap1-associating domain. In addition, translocation to the perinuclear region was induced upon association with Rap1.GTP. However, the function of the CDC25 homology domain remains to be clarified. Here we show that the CDC25 homology domain of PLCepsilon functions as a guanine nucleotide exchange factor for Rap1 but not for any other Ras family GTPases examined including Rap2 and Ha-Ras. Consistent with this, coexpression of full-length PLCepsilon or its N-terminal fragment carrying the CDC25 homology domain causes an increase of the intracellular level of Rap1.GTP. Concurrently, stimulation of the downstream kinases B-Raf and extracellular signal-regulated kinase is observed, whereas the intracellular level of Ras.GTP and Raf-1 kinase activity are unaffected. In wild-type Rap1-overexpressing cells, epidermal growth factor induces translocation of PLCepsilon to the perinuclear compartments such as the Golgi apparatus, which is sustained for at least 20 min. In contrast, PLCepsilon lacking the CDC25 domain translocates to the perinuclear compartments only transiently. Further, the formation of Rap1.GTP upon epidermal growth factor stimulation exhibits a prolonged time course in cells expressing full-length PLCepsilon compared with those expressing PLCepsilon lacking the CDC25 homology domain. These results suggest a pivotal role of the CDC25 homology domain in amplifying Rap1-dependent signal transduction, including the activation of PLCepsilon itself, at specific subcellular locations such as the Golgi apparatus.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
30301-7
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11395506-Animals, pubmed-meshheading:11395506-COS Cells, pubmed-meshheading:11395506-Cell Nucleus, pubmed-meshheading:11395506-Cytoplasm, pubmed-meshheading:11395506-Enzyme Activation, pubmed-meshheading:11395506-Gene Deletion, pubmed-meshheading:11395506-Golgi Apparatus, pubmed-meshheading:11395506-Humans, pubmed-meshheading:11395506-Microscopy, Fluorescence, pubmed-meshheading:11395506-Mitogen-Activated Protein Kinases, pubmed-meshheading:11395506-Monomeric GTP-Binding Proteins, pubmed-meshheading:11395506-Mutation, pubmed-meshheading:11395506-Phosphoinositide Phospholipase C, pubmed-meshheading:11395506-Plasmids, pubmed-meshheading:11395506-Protein Binding, pubmed-meshheading:11395506-Protein Structure, Tertiary, pubmed-meshheading:11395506-Protein Transport, pubmed-meshheading:11395506-Proto-Oncogene Proteins c-raf, pubmed-meshheading:11395506-Signal Transduction, pubmed-meshheading:11395506-Time Factors, pubmed-meshheading:11395506-Transfection, pubmed-meshheading:11395506-Type C Phospholipases, pubmed-meshheading:11395506-rap1 GTP-Binding Proteins, pubmed-meshheading:11395506-ras-GRF1
pubmed:year
2001
pubmed:articleTitle
Role of the CDC25 homology domain of phospholipase Cepsilon in amplification of Rap1-dependent signaling.
pubmed:affiliation
Division of Molecular Biology, Department of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't