Linked Life Data

15145946

Source:http://linkedlifedata.com/resource/pubmed/id/15145946

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
30
pubmed:dateCreated
2004-7-19
pubmed:abstractText
Plasma membrane calmodulin-dependent calcium ATPases (PMCAs) are enzymatic systems implicated in the extrusion of calcium from the cell. We and others have previously identified molecular interactions between the cytoplasmic COOH-terminal end of PMCA and PDZ domain-containing proteins. These interactions suggested a new role for PMCA as a modulator of signal transduction pathways. The existence of other intracellular regions in the PMCA molecule prompted us to investigate the possible participation of other domains in interactions with different partner proteins. A two-hybrid screen of a human fetal heart cDNA library, using the region 652-840 of human PMCA4b (located in the catalytic, second intracellular loop) as bait, revealed a novel interaction between PMCA4b and the tumor suppressor RASSF1, a Ras effector protein involved in H-Ras-mediated apoptosis. Immunofluorescence co-localization, immunoprecipitation, and glutathione S-transferase pull-down experiments performed in mammalian cells provided further confirmation of the physical interaction between the two proteins. The interaction domain has been narrowed down to region 74-123 of RASSF1C (144-193 in RASSF1A) and 652-748 of human PMCA4b. The functionality of this interaction was demonstrated by the inhibition of the epidermal growth factor-dependent activation of the Erk pathway when PMCA4b and RASSF1 were co-expressed. This inhibition was abolished by blocking PMCA/RASSSF1 association with an excess of a green fluorescent protein fusion protein containing the region 50-123 of RASSF1C. This work describes a novel protein-protein interaction involving a domain of PMCA other than the COOH terminus. It suggests a function for PMCA4b as an organizer of macromolecular protein complexes, where PMCA4b could recruit diverse proteins through interaction with different domains. Furthermore, the functional association with RASSF1 indicates a role for PMCA4b in the modulation of Ras-mediated signaling.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
31318-28
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:15145946-Animals, pubmed-meshheading:15145946-Apoptosis, pubmed-meshheading:15145946-Base Sequence, pubmed-meshheading:15145946-Binding Sites, pubmed-meshheading:15145946-Calcium-Transporting ATPases, pubmed-meshheading:15145946-Cation Transport Proteins, pubmed-meshheading:15145946-Cell Line, pubmed-meshheading:15145946-Cells, Cultured, pubmed-meshheading:15145946-Epidermal Growth Factor, pubmed-meshheading:15145946-Humans, pubmed-meshheading:15145946-MAP Kinase Signaling System, pubmed-meshheading:15145946-Mutagenesis, Site-Directed, pubmed-meshheading:15145946-Plasma Membrane Calcium-Transporting ATPases, pubmed-meshheading:15145946-Plasmids, pubmed-meshheading:15145946-Protein Binding, pubmed-meshheading:15145946-Rats, pubmed-meshheading:15145946-Recombinant Proteins, pubmed-meshheading:15145946-Transfection, pubmed-meshheading:15145946-Tumor Suppressor Proteins, pubmed-meshheading:15145946-Two-Hybrid System Techniques
pubmed:year
2004
pubmed:articleTitle
Novel functional interaction between the plasma membrane Ca2+ pump 4b and the proapoptotic tumor suppressor Ras-associated factor 1 (RASSF1).
pubmed:affiliation
Division of Cardiology, University of Manchester, Manchester M13 9PT, United Kingdom.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't