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http://purl.uniprot.org/citations/12882960http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12882960http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12882960http://www.w3.org/2000/01/rdf-schema#comment"Upon encountering macrophage colony-stimulating factor (M-CSF), human monocytes undergo a series of cellular signaling events leading to an increase in Akt activity. However, the regulation of these events is not completely understood. Because the inositol 5'-phosphatase SHIP-1 is an important regulator of intracellular levels of phosphatidylinositol 3,4,5-trisphosphate, an important second messenger necessary for Akt activation, we hypothesized that SHIP-1 was involved in the regulation of M-CSF receptor (M-CSF-R)-induced Akt activation. In the human monocytic cell line, THP-1, SHIP-1 became tyrosine-phosphorylated following M-CSF activation in a Src family kinase-dependent manner. Transfection of 3T3-Fms cells, which express the human M-CSF-R, with wild-type SHIP-1 showed that SHIP-1 was necessary for the negative regulation of M-CSF-induced Akt activation. In THP-1 cells, SHIP-1 bound Lyn, independent of the kinase activity of Lyn, following M-CSF activation. Utilizing a glutathione S-transferase fusion protein, we found that SHIP-1 bound to Lyn via the SHIP-1 Src homology 2 domain. Furthermore, transfection of THP-1 cells with a wild-type SHIP-1 construct reduced NF-kappaB-dependent transcriptional activation of a reporter gene, whereas a SHIP-1 Src homology 2 domain construct resulted in an increase in NF-kappaB activation. Additionally, in 3T3-Fms cells, Lyn enhanced the ability of SHIP-1 to regulate Akt activation by stabilizing SHIP-1 at the cellular membrane. Finally, macrophages isolated from both SHIP-1- and Lyn-deficient mice exhibited enhanced Akt phosphorylation following M-CSF stimulation. These data provide the first evidence of the involvement of both SHIP-1 and Lyn in the negative regulation of M-CSF-R-induced Akt activation."xsd:string
http://purl.uniprot.org/citations/12882960http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m305021200"xsd:string
http://purl.uniprot.org/citations/12882960http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m305021200"xsd:string
http://purl.uniprot.org/citations/12882960http://purl.uniprot.org/core/author"Helgason C.D."xsd:string
http://purl.uniprot.org/citations/12882960http://purl.uniprot.org/core/author"Helgason C.D."xsd:string
http://purl.uniprot.org/citations/12882960http://purl.uniprot.org/core/author"Humphries R.K."xsd:string
http://purl.uniprot.org/citations/12882960http://purl.uniprot.org/core/author"Humphries R.K."xsd:string
http://purl.uniprot.org/citations/12882960http://purl.uniprot.org/core/author"Baran C.P."xsd:string
http://purl.uniprot.org/citations/12882960http://purl.uniprot.org/core/author"Baran C.P."xsd:string
http://purl.uniprot.org/citations/12882960http://purl.uniprot.org/core/author"Krystal G."xsd:string
http://purl.uniprot.org/citations/12882960http://purl.uniprot.org/core/author"Krystal G."xsd:string
http://purl.uniprot.org/citations/12882960http://purl.uniprot.org/core/author"Marsh C.B."xsd:string
http://purl.uniprot.org/citations/12882960http://purl.uniprot.org/core/author"Marsh C.B."xsd:string
http://purl.uniprot.org/citations/12882960http://purl.uniprot.org/core/author"Tridandapani S."xsd:string
http://purl.uniprot.org/citations/12882960http://purl.uniprot.org/core/author"Tridandapani S."xsd:string
http://purl.uniprot.org/citations/12882960http://purl.uniprot.org/core/date"2003"xsd:gYear
http://purl.uniprot.org/citations/12882960http://purl.uniprot.org/core/date"2003"xsd:gYear
http://purl.uniprot.org/citations/12882960http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/12882960http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/12882960http://purl.uniprot.org/core/pages"38628-38636"xsd:string
http://purl.uniprot.org/citations/12882960http://purl.uniprot.org/core/pages"38628-38636"xsd:string
http://purl.uniprot.org/citations/12882960http://purl.uniprot.org/core/title"The inositol 5'-phosphatase SHIP-1 and the Src kinase Lyn negatively regulate macrophage colony-stimulating factor-induced Akt activity."xsd:string
http://purl.uniprot.org/citations/12882960http://purl.uniprot.org/core/title"The inositol 5'-phosphatase SHIP-1 and the Src kinase Lyn negatively regulate macrophage colony-stimulating factor-induced Akt activity."xsd:string
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