Linked Life Data

11390389

Source:http://linkedlifedata.com/resource/pubmed/id/11390389

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
31
pubmed:dateCreated
2001-7-30
pubmed:abstractText
Phospholipid scramblase 1 (PLSCR1) is a plasma membrane protein that has been proposed to play a role in the transbilayer movement of plasma membrane phospholipids. PLSCR1 contains multiple proline-rich motifs resembling Src homology 3 (SH3) domain-binding sites. An initial screen against 13 different SH3 domains revealed a marked specificity of PLSCR1 for binding to the Abl SH3 domain. Binding between intracellular PLSCR1 and c-Abl was demonstrated by co-immunoprecipitation of both proteins from several cell lines. Deletion of the proline-rich segment in PLSCR1 (residues 1--118) abolished its binding to the Abl SH3 domain. PLSCR1 was Tyr-phosphorylated by c-Abl in vitro. Phosphorylation was abolished by mutation of Tyr residues Tyr(69)/Tyr(74) within the tandem repeat sequence (68)VYNQPVYNQP(77) of PLSCR1, implying that these residues are the likely sites of phosphorylation. Cellular PLSCR1 was found to be constitutively Tyr-phosphorylated in several cell lines. The Tyr phosphorylation of PLSCR1 was increased upon overexpression of c-Abl and significantly reduced either upon cell treatment with the Abl kinase inhibitor STI571, or in Abl-/- mouse fibroblasts, suggesting that cellular PLSCR1 is a normal substrate of c-Abl. Cell treatment with the DNA-damaging agent cisplatin activated c-Abl kinase and increased Tyr phosphorylation of PLSCR1. The cisplatin-induced phosphorylation of PLSCR1 was inhibited by STI571 and was not observed in Abl-/- fibroblasts. These findings indicate that c-Abl binds and phosphorylates PLSCR1, and raise the possibility that an interaction between c-Abl and plasma membrane PLSCR1 might contribute to the cellular response to genotoxic stress.
pubmed:grant
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
3
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
28984-90
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11390389-Amino Acid Sequence, pubmed-meshheading:11390389-Amino Acid Substitution, pubmed-meshheading:11390389-Animals, pubmed-meshheading:11390389-Binding Sites, pubmed-meshheading:11390389-Carrier Proteins, pubmed-meshheading:11390389-Cell Line, pubmed-meshheading:11390389-Cells, Cultured, pubmed-meshheading:11390389-Fibroblasts, pubmed-meshheading:11390389-Genes, abl, pubmed-meshheading:11390389-Glutathione Transferase, pubmed-meshheading:11390389-Humans, pubmed-meshheading:11390389-Membrane Proteins, pubmed-meshheading:11390389-Mice, pubmed-meshheading:11390389-Mice, Knockout, pubmed-meshheading:11390389-Mutagenesis, Site-Directed, pubmed-meshheading:11390389-Phospholipid Transfer Proteins, pubmed-meshheading:11390389-Phospholipids, pubmed-meshheading:11390389-Phosphorylation, pubmed-meshheading:11390389-Protein Binding, pubmed-meshheading:11390389-Proto-Oncogene Proteins c-abl, pubmed-meshheading:11390389-Recombinant Fusion Proteins, pubmed-meshheading:11390389-Repetitive Sequences, Amino Acid, pubmed-meshheading:11390389-Transfection, pubmed-meshheading:11390389-Tyrosine, pubmed-meshheading:11390389-src Homology Domains
pubmed:year
2001
pubmed:articleTitle
c-Abl tyrosine kinase binds and phosphorylates phospholipid scramblase 1.
pubmed:affiliation
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't