PubMed:7539137
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/7539137","sourcedb":"PubMed","sourceid":"7539137","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/7539137","text":"Identification of an 11-kDa FKBP12-rapamycin-binding domain within the 289-kDa FKBP12-rapamycin-associated protein and characterization of a critical serine residue.\nComplexed with its intracellular receptor, FKBP12, the natural product rapamycin inhibits G1 progression of the cell cycle in a variety of mammalian cell lines and in the yeast Saccharomyces cerevisae. Previously, a mammalian protein that directly associates with FKBP12-rapamycin has been identified and its encoding gene has been cloned from both human (designated FRAP) [Brown, E.J., Albers, M.W., Shin, T.B., Ichikawa, K., Keith, C.T., Lane, W.S. \u0026 Schreiber, S.L. (1994) Nature (London) 369, 756-758] and rat (designated RAFT) [Sabatini, D.M., Erdjument-Bromage, H., Lui, M., Tempst, P. \u0026 Snyder, S.H. (1994) Cell 78, 35-43]. The full-length FRAP is a 289-kDa protein containing a putative phosphatidylinositol kinase domain. Using an in vitro transcription/translation assay method coupled with proteolysis studies, we have identified an 11-kDa FKBP12-rapamycin-binding domain within FRAP. This minimal binding domain lies N-terminal to the kinase domain and spans residues 2025-2114. In addition, we have carried out mutagenesis studies to investigate the role of Ser2035, a potential phosphorylation site for protein kinase C within this domain. We now show that the FRAP Ser2035--\u003eAla mutant displays similar binding affinity when compared with the wild-type protein, whereas all other mutations at this site, including mimics of phosphoserine, abolish binding, presumably due to either unfavorable steric interactions or induced conformational changes.","tracks":[{"project":"AIMed","denotations":[{"id":"T1","span":{"begin":28,"end":34},"obj":"protein"},{"id":"T2","span":{"begin":79,"end":114},"obj":"protein"},{"id":"T3","span":{"begin":209,"end":215},"obj":"protein"},{"id":"T4","span":{"begin":430,"end":436},"obj":"protein"},{"id":"T5","span":{"begin":533,"end":537},"obj":"protein"},{"id":"T6","span":{"begin":692,"end":696},"obj":"protein"},{"id":"T7","span":{"begin":813,"end":817},"obj":"protein"},{"id":"T8","span":{"begin":1017,"end":1023},"obj":"protein"},{"id":"T9","span":{"begin":1056,"end":1060},"obj":"protein"},{"id":"T10","span":{"begin":1283,"end":1299},"obj":"protein"},{"id":"T11","span":{"begin":1341,"end":1345},"obj":"protein"}],"attributes":[{"subj":"T1","pred":"source","obj":"AIMed"},{"subj":"T2","pred":"source","obj":"AIMed"},{"subj":"T3","pred":"source","obj":"AIMed"},{"subj":"T4","pred":"source","obj":"AIMed"},{"subj":"T5","pred":"source","obj":"AIMed"},{"subj":"T6","pred":"source","obj":"AIMed"},{"subj":"T7","pred":"source","obj":"AIMed"},{"subj":"T8","pred":"source","obj":"AIMed"},{"subj":"T9","pred":"source","obj":"AIMed"},{"subj":"T10","pred":"source","obj":"AIMed"},{"subj":"T11","pred":"source","obj":"AIMed"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"AIMed","color":"#93ecd8","default":true}]}]}}