Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-1-14
pubmed:abstractText
Ras guanine nucleotide-releasing protein 4 (RasGRP4) is a mast cell (MC)-restricted guanine nucleotide exchange factor and diacylglycerol (DAG)/phorbol ester receptor. An RasGRP4-defective variant of the human MC line HMC-1 was used to create stable clones expressing green fluorescent protein-labeled RasGRP4 for monitoring the movement of this protein inside MCs after exposure to phorbol 12-myristate 13-acetate (PMA), and for evaluating the protein's ability to control gene expression. RasGRP4 resided primarily in the cytosol. After exposure to PMA, RasGRP4 quickly translocated to the inner leaflet of the cell's plasma membrane. 15-30 min later, this signaling protein translocated from the plasma membrane to other intracellular sites. The translocation of RasGRP4 from the cytosol to its varied membrane compartments was found to be highly dependent on Phe(548) in the protein's C1 DAG/PMA-binding domain. Extracellular signal-regulated kinases 1 and 2 were activated during this translocation process, and c-kit/CD117 was lost from the cell's surface. Transcript-profiling approaches revealed that RasGRP4 profoundly regulated the expression of hundreds of genes in HMC-1 cells. For example, the expression of the transcript that encodes the interleukin (IL) 13 receptor IL-13Ralpha2 increased 61- to 860-fold in RasGRP4-expressing HMC-1 cells. A marked increase in IL-13Ralpha2 protein levels also was found. The accumulated data suggest RasGRP4 translocates to varied intracellular compartments via its DAG/PMA-binding domain to regulate signaling pathways that control gene and protein expression in MCs, including the cell's ability to respond to IL-13.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Diglycerides, http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-13, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-13 Receptor alpha2..., http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-kit, http://linkedlifedata.com/resource/pubmed/chemical/RASGRP4 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins, http://linkedlifedata.com/resource/pubmed/chemical/STAT6 Transcription Factor, http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate, http://linkedlifedata.com/resource/pubmed/chemical/ras Guanine Nucleotide Exchange...
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
283
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1610-21
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18024961-Cell Line, pubmed-meshheading:18024961-Diglycerides, pubmed-meshheading:18024961-Endocytosis, pubmed-meshheading:18024961-Gene Expression Profiling, pubmed-meshheading:18024961-Gene Expression Regulation, pubmed-meshheading:18024961-Green Fluorescent Proteins, pubmed-meshheading:18024961-Humans, pubmed-meshheading:18024961-Interleukin-13, pubmed-meshheading:18024961-Interleukin-13 Receptor alpha2 Subunit, pubmed-meshheading:18024961-Mast Cells, pubmed-meshheading:18024961-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:18024961-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:18024961-Phenotype, pubmed-meshheading:18024961-Phosphorylation, pubmed-meshheading:18024961-Protein Transport, pubmed-meshheading:18024961-Proto-Oncogene Proteins c-kit, pubmed-meshheading:18024961-RNA, Messenger, pubmed-meshheading:18024961-Recombinant Fusion Proteins, pubmed-meshheading:18024961-STAT6 Transcription Factor, pubmed-meshheading:18024961-Tetradecanoylphorbol Acetate, pubmed-meshheading:18024961-ras Guanine Nucleotide Exchange Factors
pubmed:year
2008
pubmed:articleTitle
The Diacylglycerol-dependent translocation of ras guanine nucleotide-releasing protein 4 inside a human mast cell line results in substantial phenotypic changes, including expression of interleukin 13 receptor alpha2.
pubmed:affiliation
Department of Medicine, University of New South Wales, St. George Hospital, 2 South St. Centre, New South Wales 2217, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural