Source:http://linkedlifedata.com/resource/pubmed/id/17580302
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
34
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pubmed:dateCreated |
2007-8-20
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pubmed:abstractText |
AKT kinase, also known as protein kinase B, is a key regulator of cell growth, proliferation, and metabolism. The activation of the AKT signaling pathway is one of the most frequent molecular alterations in a wide variety of human cancers. Dickson and coworkers recently observed that Ca(2+).calmodulin (Ca(2+).CaM) may be a common regulator of AKT1 activation (Deb, T. B., Coticchia, C. M., and Dickson, R. B. (2004) J. Biol. Chem. 279, 38903-38911). In our efforts to scan the mRNA-displayed proteome libraries for Ca(2+).CaM-binding proteins, we found that both human and Caenorhabditis elegans AKT1 kinases bound to CaM in a Ca(2+)-dependent manner (Shen, X., Valencia, C. A., Szostak, J., Dong, B., and Liu, R. (2005) Proc. Natl. Acad. Sci. U. S. A. 102, 5969-5974 and Shen, X., Valencia, C. A., Gao, W., Cotten, S. W., Dong, B., Chen, M., and Liu, R. (2007) submitted for publication). Here we demonstrate that Ca(2+).CaM and human AKT1 were efficiently co-immunoprecipitated, and their interaction was direct rather than mediated by other proteins. The binding is in part attributed to the first 42 residues of the pleckstrin homology (PH) domain, a region that is critical for the recognition of its lipid ligands. The PH domain of human AKT1 can disrupt the complex of the full-length AKT1 with Ca(2+).CaM. In addition, Ca(2+).CaM competes with phosphatidylinositol 3,4,5-trisphophate for interaction with the PH domain of human AKT1. Our findings suggest that Ca(2+).CaM is directly involved in regulating the functions of AKT1, presumably by releasing the activated AKT1 from the plasma membrane and/or prohibiting it from re-association with phosphoinositides on plasma membrane.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Blood Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calmodulin,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/platelet protein P47
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
24
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pubmed:volume |
282
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
25131-40
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17580302-Amino Acid Sequence,
pubmed-meshheading:17580302-Animals,
pubmed-meshheading:17580302-Binding, Competitive,
pubmed-meshheading:17580302-Blood Proteins,
pubmed-meshheading:17580302-Caenorhabditis elegans,
pubmed-meshheading:17580302-Calcium,
pubmed-meshheading:17580302-Calmodulin,
pubmed-meshheading:17580302-Cell Membrane,
pubmed-meshheading:17580302-Cell Proliferation,
pubmed-meshheading:17580302-HeLa Cells,
pubmed-meshheading:17580302-Humans,
pubmed-meshheading:17580302-Molecular Sequence Data,
pubmed-meshheading:17580302-Phosphoproteins,
pubmed-meshheading:17580302-Protein Binding,
pubmed-meshheading:17580302-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:17580302-Sequence Homology, Amino Acid
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pubmed:year |
2007
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pubmed:articleTitle |
Ca(2+)/calmodulin directly interacts with the pleckstrin homology domain of AKT1.
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pubmed:affiliation |
School of Pharmacy and Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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