| http://purl.uniprot.org/citations/17446348 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17446348 | http://www.w3.org/2000/01/rdf-schema#comment | "In acute myeloid leukemia (AML), mutational activation of the receptor tyrosine kinase (RTK) Flt3 is frequently involved in leukemic transformation. However, little is known about a possible role of highly expressed wild-type Flt3 in AML. The proto-oncogene c-Cbl is an important regulator of RTK signaling, acting through its ubiquitin ligase activity and as a platform for several signaling adaptor molecules. Here, we analyzed the role of c-Cbl in Flt3 signal transduction and myeloid transformation. C-Cbl physically interacted with Flt3 and was tyrosine phosphorylated in the presence of Flt3-ligand (FL). Overexpression of a dominant-negative form of c-Cbl (Cbl-70Z) inhibited FL-induced Flt3 ubiquitylation and internalization, indicating involvement of c-Cbl in Flt3 signaling. DNA sequencing of AML bone marrow revealed a case with a c-Cbl point mutation (Cbl-R420Q). Cbl-R420Q inhibited Flt3 internalization and ubiquitylation. Coexpression of Cbl-R420Q or Cbl-70Z with Flt3 induced cytokine-independent growth and survival of 32Dcl3 cells in the absence of FL. Also, the mutant Cbl proteins altered the amplitude and duration of Flt3-dependent signaling events. Our results indicate an important role of Cbl proteins in Flt3 signal modulation. Also, the data suggest a novel mechanism of leukemic transformation in AML by mutational inactivation of negative RTK regulators."xsd:string |
| http://purl.uniprot.org/citations/17446348 | http://purl.org/dc/terms/identifier | "doi:10.1182/blood-2007-01-066076"xsd:string |
| http://purl.uniprot.org/citations/17446348 | http://purl.uniprot.org/core/author | "Choudhary C."xsd:string |
| http://purl.uniprot.org/citations/17446348 | http://purl.uniprot.org/core/author | "Duyster J."xsd:string |
| http://purl.uniprot.org/citations/17446348 | http://purl.uniprot.org/core/author | "Dikic I."xsd:string |
| http://purl.uniprot.org/citations/17446348 | http://purl.uniprot.org/core/author | "Berdel W.E."xsd:string |
| http://purl.uniprot.org/citations/17446348 | http://purl.uniprot.org/core/author | "Muller-Tidow C."xsd:string |
| http://purl.uniprot.org/citations/17446348 | http://purl.uniprot.org/core/author | "Sargin B."xsd:string |
| http://purl.uniprot.org/citations/17446348 | http://purl.uniprot.org/core/author | "Schwable J."xsd:string |
| http://purl.uniprot.org/citations/17446348 | http://purl.uniprot.org/core/author | "Serve H."xsd:string |
| http://purl.uniprot.org/citations/17446348 | http://purl.uniprot.org/core/author | "Koschmieder S."xsd:string |
| http://purl.uniprot.org/citations/17446348 | http://purl.uniprot.org/core/author | "Tickenbrock L."xsd:string |
| http://purl.uniprot.org/citations/17446348 | http://purl.uniprot.org/core/author | "Crosetto N."xsd:string |
| http://purl.uniprot.org/citations/17446348 | http://purl.uniprot.org/core/author | "Grundler R."xsd:string |
| http://purl.uniprot.org/citations/17446348 | http://purl.uniprot.org/core/author | "August B."xsd:string |
| http://purl.uniprot.org/citations/17446348 | http://purl.uniprot.org/core/author | "Brandts C."xsd:string |
| http://purl.uniprot.org/citations/17446348 | http://purl.uniprot.org/core/author | "Schmidt M.H.H."xsd:string |
| http://purl.uniprot.org/citations/17446348 | http://purl.uniprot.org/core/author | "Bandi S.R."xsd:string |
| http://purl.uniprot.org/citations/17446348 | http://purl.uniprot.org/core/author | "Rensinghoff M."xsd:string |
| http://purl.uniprot.org/citations/17446348 | http://purl.uniprot.org/core/author | "Thiessen C."xsd:string |
| http://purl.uniprot.org/citations/17446348 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/17446348 | http://purl.uniprot.org/core/name | "Blood"xsd:string |
| http://purl.uniprot.org/citations/17446348 | http://purl.uniprot.org/core/pages | "1004-1012"xsd:string |
| http://purl.uniprot.org/citations/17446348 | http://purl.uniprot.org/core/title | "Flt3-dependent transformation by inactivating c-Cbl mutations in AML."xsd:string |