Linked Life Data

15016827

Source:http://linkedlifedata.com/resource/pubmed/id/15016827

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2004-5-17
pubmed:abstractText
Protein phosphatase-1 (PP1) catalytic subunit isoforms interact with diverse proteins, typically containing a canonical (R/K)(V/I)XF motif. Despite sharing approximately 90% amino acid sequence identity, PP1beta and PP1gamma1 have distinct subcellular localizations that may be determined by selective interactions with PP1-binding proteins. Immunoprecipitation studies from brain and muscle extracts demonstrated that PP1gamma1 selectively interacts with spinophilin and neurabin, F-actin-targeting proteins, whereas PP1beta selectively interacted with G(M)/R(GL), the striated-muscle glycogen-targeting subunit. Glutathione S-transferase (GST) fusion proteins containing residues 146-493 of neurabin (GST-Nb-(146-493)) or residues 1-240 of G(M)/R(GL) (GST-G(M)-(1-240)) recapitulated these isoform selectivities in binding and phosphatase activity inhibition assays. Site-directed mutagenesis indicated that this isoform selectivity was not due to sequence differences between the canonical PP1-binding motifs (neurabin, (457)KIKF(460); G(M)/R(GL), (65)RVSF(68)). A chimeric GST fusion protein containing residues 1-64 of G(M)/R(GL) fused to residues 457-493 of neurabin (GST-G(M)/Nb) selectively bound to and inhibited PP1gamma1, whereas a GST-Nb/G(M) chimera containing Nb-(146-460) fused to G(M)-(69-240) selectively interacted with and weakly inhibited PP1beta, implicating domain(s) C-terminal to the (R/K)(V/I)XF motif as determinants of PP1 isoform selectivity. Deletion of Pro(464) and Ile(465) in neurabin (deltaPI) to equally space a conserved cluster of amino acids from the (R/K)(V/I)XF motif as in G(M)/R(GL) severely compromised the ability of neurabin to bind and inhibit both isoforms but did not affect PP1gamma1 selectivity. Further analysis of a series of C-terminal truncated GST-Nb-(146-493) proteins identified residues 473-479 of neurabin as containing a crucial PP1gamma1-selectivity determinant. In combination, these data identify a novel PP1gamma1-selective interaction domain in neurabin that may allow for selective regulation and/or subcellular targeting of PP1 isoforms.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
21714-23
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:15016827-Actins, pubmed-meshheading:15016827-Amino Acid Motifs, pubmed-meshheading:15016827-Amino Acid Sequence, pubmed-meshheading:15016827-Animals, pubmed-meshheading:15016827-Blotting, Western, pubmed-meshheading:15016827-Brain, pubmed-meshheading:15016827-Catalytic Domain, pubmed-meshheading:15016827-Dendrites, pubmed-meshheading:15016827-Dose-Response Relationship, Drug, pubmed-meshheading:15016827-Gene Deletion, pubmed-meshheading:15016827-Genetic Vectors, pubmed-meshheading:15016827-Glutathione Transferase, pubmed-meshheading:15016827-Mice, pubmed-meshheading:15016827-Microfilament Proteins, pubmed-meshheading:15016827-Molecular Sequence Data, pubmed-meshheading:15016827-Muscles, pubmed-meshheading:15016827-Mutagenesis, Site-Directed, pubmed-meshheading:15016827-Mutation, pubmed-meshheading:15016827-Nerve Tissue Proteins, pubmed-meshheading:15016827-Phosphoprotein Phosphatases, pubmed-meshheading:15016827-Precipitin Tests, pubmed-meshheading:15016827-Protein Binding, pubmed-meshheading:15016827-Protein Isoforms, pubmed-meshheading:15016827-Protein Phosphatase 1, pubmed-meshheading:15016827-Protein Structure, Tertiary, pubmed-meshheading:15016827-Rats, pubmed-meshheading:15016827-Recombinant Fusion Proteins, pubmed-meshheading:15016827-Recombinant Proteins, pubmed-meshheading:15016827-Sequence Homology, Amino Acid
pubmed:year
2004
pubmed:articleTitle
A protein phosphatase-1gamma1 isoform selectivity determinant in dendritic spine-associated neurabin.
pubmed:affiliation
Department of Molecular Physiology and Biophysics, The Center for Molecular Neuroscience, and The Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0615, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.