Linked Life Data

15140879

Source:http://linkedlifedata.com/resource/pubmed/id/15140879

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2004-5-31
pubmed:abstractText
The regulation of the multifunctional calcium/calmodulin dependent protein kinase II (CaMKII) by serine/threonine protein phosphatases has been extensively studied in neuronal cells; however, this regulation has not been investigated previously in fibroblasts. We cloned a cDNA from SV40-transformed human fibroblasts that shares 80% homology to a rat calcium/calmodulin-dependent protein kinase phosphatase that encodes a PPM1F protein. By using extracts from transfected cells, PPM1F, but not a mutant (R326A) in the conserved catalytic domain, was found to dephosphorylate in vitro a peptide corresponding to the auto-inhibitory region of CaMKII. Further analyses demonstrated that PPM1F specifically dephosphorylates the phospho-Thr-286 in autophosphorylated CaMKII substrate and thus deactivates the CaMKII in vitro. Coimmunoprecipitation of CaMKII with PPM1F indicates that the two proteins can interact intracellularly. Binding of PPM1F to CaMKII involves multiple regions and is not dependent on intact phosphatase activity. Furthermore, overexpression of PPM1F in fibroblasts caused a reduction in the CaMKII-specific phosphorylation of the known substrate vimentin(Ser-82) following induction of the endogenous CaM kinase. These results identify PPM1F as a CaM kinase phosphatase within fibroblasts, although it may have additional functions intracellularly since it has been presented elsewhere as POPX2 and hFEM-2. We conclude that PPM1F, possibly together with the other previously described protein phosphatases PP1 and PP2A, can regulate the activity of CaMKII. Moreover, because PPM1F dephosphorylates the critical autophosphorylation site of CaMKII, we propose that this phosphatase plays a key role in the regulation of the kinase intracellularly.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
4
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
24889-98
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:15140879-Animals, pubmed-meshheading:15140879-Binding Sites, pubmed-meshheading:15140879-Calcium-Calmodulin-Dependent Protein Kinase Type 2, pubmed-meshheading:15140879-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:15140879-Catalytic Domain, pubmed-meshheading:15140879-Cell Line, pubmed-meshheading:15140879-Cloning, Molecular, pubmed-meshheading:15140879-DNA, Complementary, pubmed-meshheading:15140879-Fibroblasts, pubmed-meshheading:15140879-Gene Deletion, pubmed-meshheading:15140879-Gene Expression Regulation, Enzymologic, pubmed-meshheading:15140879-Humans, pubmed-meshheading:15140879-Mice, pubmed-meshheading:15140879-Mutation, pubmed-meshheading:15140879-NIH 3T3 Cells, pubmed-meshheading:15140879-Neurons, pubmed-meshheading:15140879-Peptides, pubmed-meshheading:15140879-Phosphoprotein Phosphatases, pubmed-meshheading:15140879-Phosphorylation, pubmed-meshheading:15140879-Precipitin Tests, pubmed-meshheading:15140879-Protein Binding, pubmed-meshheading:15140879-Rats, pubmed-meshheading:15140879-Serine, pubmed-meshheading:15140879-Threonine, pubmed-meshheading:15140879-Time Factors, pubmed-meshheading:15140879-Transfection, pubmed-meshheading:15140879-Vimentin
pubmed:year
2004
pubmed:articleTitle
Regulation of the multifunctional Ca2+/calmodulin-dependent protein kinase II by the PP2C phosphatase PPM1F in fibroblasts.
pubmed:affiliation
Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey (UMDNJ)-New Jersey Medical School and UMDNJ-Graduate School of Biomedical Sciences, Newark, New Jersey 07101, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.