Linked Life Data

9619827

Source:http://linkedlifedata.com/resource/pubmed/id/9619827

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
1998-6-16
pubmed:abstractText
The SH2 and SH3 binding partner AFAP-110 is a tyrosine phosphorylated substrate of Src. AFAP-110 has been hypothesized to link Src to actin filaments, which may contribute to the effects of Src upon actin filament integrity. However, it has been unclear what effect activated Src (Src527F) has upon AFAP-110 structure or function and whether AFAP-110 plays a role in actin filament integrity. We report here that the carboxy terminal 127 amino acids of AFAP-110 are comprised of an alpha-helical region that contains a leucine zipper motif. This indicated the potential of AFAP-110 to self-associate. Expression of the carboxy terminus as a fusion protein (GST-cterm) will permit affinity absorption of cellular AFAP-110. The integrity of the alpha-helical leucine zipper motif in GST-cterm is required for affinity absorption, but binding is not due to a classical leucine zipper interaction. Co-expression of Src527F, unlike cSrc, will abrogate affinity absorption of AFAP-110 with GST-cterm. These data indicate that Src527F has affected a change in the carboxy terminal structure that renders AFAP-110 unavailable for affinity absorption. Superose chromatography demonstrate that AFAP-110 will fractionate as a monomer or multimer, indicating AFAP-110 can be detected in a self-associated form in cell lysates. Co-expression of Src527F resulted in AFAP-110 fractionating with a molecular weight that predicts only a multimeric population. Deletional mutagenesis also indicate a biological role for the carboxy terminus in cellular localization and actin filament integrity. Deletion of the entire carboxy terminal alpha-helix (84 amino acids) will not permit AFAP-110 to efficiently colocalize with actin filaments or the cell membrane. Deletion of only the leucine zipper region of the carboxy terminal alpha-helix (44 amino acids) from AFAP-110 (AFAPAdeltazip) demonstrate that both AFAPdeltalzip and actin filaments are repositioned into rosette-like structures, similar to the effects of Src527F, while co-expression of AFAP-110 with cSrc will not affect actin filaments. These data indicate that AFAP-110 can play an important role in modulating actin filament integrity through carboxy terminal interactions that can be affected by Src527F.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2185-95
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:9619827-Actin Cytoskeleton, pubmed-meshheading:9619827-Actins, pubmed-meshheading:9619827-Amino Acid Sequence, pubmed-meshheading:9619827-Animals, pubmed-meshheading:9619827-COS Cells, pubmed-meshheading:9619827-Cell-Free System, pubmed-meshheading:9619827-Chromatography, Affinity, pubmed-meshheading:9619827-Gene Expression, pubmed-meshheading:9619827-Glutathione Transferase, pubmed-meshheading:9619827-Leucine Zippers, pubmed-meshheading:9619827-Microfilament Proteins, pubmed-meshheading:9619827-Molecular Sequence Data, pubmed-meshheading:9619827-Phosphoproteins, pubmed-meshheading:9619827-Protein Binding, pubmed-meshheading:9619827-Protein Structure, Secondary, pubmed-meshheading:9619827-Recombinant Fusion Proteins, pubmed-meshheading:9619827-Sequence Homology, Amino Acid, pubmed-meshheading:9619827-Subcellular Fractions, pubmed-meshheading:9619827-src-Family Kinases
pubmed:year
1998
pubmed:articleTitle
Src can regulate carboxy terminal interactions with AFAP-110, which influence self-association, cell localization and actin filament integrity.
pubmed:affiliation
The Mary Babb Randolph Cancer Center and the Department of Microbiology and Immunology, West Virginia University, Morgantown 26506-9300, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't