Linked Life Data

17088250

Source:http://linkedlifedata.com/resource/pubmed/id/17088250

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-1-8
pubmed:abstractText
Spectrin tetramers are cytoskeletal proteins required in the formation of complex animal tissues. Mammalian alphaII- and betaII-spectrin subunits form dimers that associate head to head with high affinity to form tetramers, but it is not known if this interaction is regulated. We show here that the short C-terminal splice variant of betaII-spectrin (betaIISigma2) is a substrate for phosphorylation. In vitro, protein kinase CK2 phosphorylates Ser-2110 and Thr-2159; protein kinase A phosphorylates Thr-2159. Antiphospho-Thr-2159 peptide antibody detected phosphorylated betaIISigma2 in Cos-1 cells. Immunoreactivity was increased in Cos-1 cells by treatment with forskolin, indicating that phosphorylation is promoted by elevated cAMP. The effect of forskolin was counteracted by the cAMP-dependent kinase inhibitor, H89. In vitro, protein kinase A phosphorylation of an active fragment of betaIISigma2 greatly reduced its interaction with alphaII-spectrin at the tetramerization site. Mutation of Thr-2159 to alanine eliminated inhibition by phosphorylation. Among the processes that require spectrin in mammals is the formation of neurites (incipient nerve axons). We tested the relationship of spectrin phosphorylation to neuritogenesis by transfecting the neuronal cell line, PC12, with enhanced green fluorescent protein-coupled fragments of betaIISigma2-spectrin predicted to act as inhibitors of spectrin tetramer formation. Both wild-type and T2159E mutant fragments allowed normal neuritogenesis in PC12 cells in response to nerve growth factor. The mutant T2159A inhibited neuritogenesis. Because the T2159A mutant represents a high affinity inhibitor of tetramer formation, we conclude that tetramers are requisite for neuritogenesis. Furthermore, because both the T2159E mutant and the wild-type allow neuritogenesis, we conclude that the short C-terminal betaII-spectrin is phosphorylated during this process.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
888-96
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17088250-Amino Acid Sequence, pubmed-meshheading:17088250-Animals, pubmed-meshheading:17088250-Antibodies, pubmed-meshheading:17088250-COS Cells, pubmed-meshheading:17088250-Casein Kinase II, pubmed-meshheading:17088250-Cercopithecus aethiops, pubmed-meshheading:17088250-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:17088250-Dimerization, pubmed-meshheading:17088250-Humans, pubmed-meshheading:17088250-Molecular Sequence Data, pubmed-meshheading:17088250-Neurites, pubmed-meshheading:17088250-Neurons, pubmed-meshheading:17088250-PC12 Cells, pubmed-meshheading:17088250-Phosphorylation, pubmed-meshheading:17088250-Protein Structure, Quaternary, pubmed-meshheading:17088250-Protein Structure, Tertiary, pubmed-meshheading:17088250-Rats, pubmed-meshheading:17088250-Recombinant Proteins, pubmed-meshheading:17088250-Spectrin, pubmed-meshheading:17088250-Threonine, pubmed-meshheading:17088250-Transfection
pubmed:year
2007
pubmed:articleTitle
Phosphorylation of a threonine unique to the short C-terminal isoform of betaII-spectrin links regulation of alpha-beta spectrin interaction to neuritogenesis.
pubmed:affiliation
Department of Biosciences, University of Kent, Canterbury, Kent, CT2 7NJ, Great Britain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't