Linked Life Data

19839650

Source:http://linkedlifedata.com/resource/pubmed/id/19839650

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
46
pubmed:dateCreated
2009-11-17
pubmed:abstractText
SH2 domain-containing inositol 5-phosphatases 1 (SHIP1) and 2 (SHIP2) are structurally similar proteins that catalyze the degradation of lipid secondary messenger phosphatidylinositol 3,4,5-triphosphate to produce phosphatidylinositol 3,4-diphosphate. Despite their high sequence identity (51%), SHIP1 and SHIP2 share little overlap in their in vivo functions. In this work, the sequence specificity of the SHIP2 SH2 domain was systematically defined through the screening of a combinatorial pY peptide library. Comparison of its specificity profile with that of the SHIP1 SH2 domain showed that the two SH2 domains have similar specificities, both recognizing pY peptides of the consensus sequence pY[S/Y][L/Y/M][L/M/I/V], although there are also subtle differences such as the tolerance of an arginine at the pY + 1 position by the SHIP2 but not SHIP1 SH2 domain. Surface plasmon resonance analysis of their interaction with various pY peptides suggested that the two domains have similar binding affinities but dramatically different binding kinetics, with the SHIP1 SH2 domain having fast association and dissociation rates while the SHIP2 domain showing apparent slow-binding behavior. Site-directed mutagenesis and kinetic studies indicated that the SHIP2 SH2 domain exists as a mixture of two conformational isomers. The major, inactive isomer apparently contains two cis peptidyl-prolyl bonds at positions 88 and 105, whereas the minor, active isomer has both proline residues in their trans configuration. Cis-trans isomerization of the peptidyl-prolyl bonds may provide a potential mechanism for regulating the interaction between SHIP2 and pY proteins. These data suggest that a combination of tissue distribution, specificity, and kinetic differences is likely responsible for their in vivo functional differences.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1520-4995
pubmed:author
pubmed:issnType
Electronic
pubmed:day
24
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11075-83
pubmed:meshHeading
pubmed-meshheading:19839650-Amino Acid Sequence, pubmed-meshheading:19839650-Amino Acid Substitution, pubmed-meshheading:19839650-Catalytic Domain, pubmed-meshheading:19839650-Humans, pubmed-meshheading:19839650-Kinetics, pubmed-meshheading:19839650-Ligands, pubmed-meshheading:19839650-Models, Chemical, pubmed-meshheading:19839650-Molecular Sequence Data, pubmed-meshheading:19839650-Peptide Library, pubmed-meshheading:19839650-Peptides, pubmed-meshheading:19839650-Phosphoric Monoester Hydrolases, pubmed-meshheading:19839650-Protein Binding, pubmed-meshheading:19839650-Protein Conformation, pubmed-meshheading:19839650-Recombinant Proteins, pubmed-meshheading:19839650-Sequence Homology, Amino Acid, pubmed-meshheading:19839650-Substrate Specificity, pubmed-meshheading:19839650-Surface Plasmon Resonance, pubmed-meshheading:19839650-src Homology Domains
pubmed:year
2009
pubmed:articleTitle
The SH2 domains of inositol polyphosphate 5-phosphatases SHIP1 and SHIP2 have similar ligand specificity but different binding kinetics.
pubmed:affiliation
Department of Chemistry and Ohio State Biochemistry Program, The Ohio State University, 100 West 18th Avenue, Columbus, Ohio 43210, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural