Matches in SemOpenAlex for { <https://semopenalex.org/work/W2031720246> ?p ?o ?g. }
- W2031720246 endingPage "1012" @default.
- W2031720246 startingPage "1004" @default.
- W2031720246 abstract "Abstract 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." @default.
- W2031720246 created "2016-06-24" @default.
- W2031720246 creator A5005641797 @default.
- W2031720246 creator A5006354413 @default.
- W2031720246 creator A5006392989 @default.
- W2031720246 creator A5011125993 @default.
- W2031720246 creator A5016136160 @default.
- W2031720246 creator A5025105470 @default.
- W2031720246 creator A5028388949 @default.
- W2031720246 creator A5047947852 @default.
- W2031720246 creator A5056843845 @default.
- W2031720246 creator A5065037874 @default.
- W2031720246 creator A5068695924 @default.
- W2031720246 creator A5069832311 @default.
- W2031720246 creator A5075606110 @default.
- W2031720246 creator A5082559625 @default.
- W2031720246 creator A5082589698 @default.
- W2031720246 creator A5082730369 @default.
- W2031720246 creator A5086016311 @default.
- W2031720246 creator A5088789978 @default.
- W2031720246 date "2007-08-01" @default.
- W2031720246 modified "2023-10-10" @default.
- W2031720246 title "Flt3-dependent transformation by inactivating c-Cbl mutations in AML" @default.
- W2031720246 cites W1542395305 @default.
- W2031720246 cites W1571287379 @default.
- W2031720246 cites W1624856187 @default.
- W2031720246 cites W1639582946 @default.
- W2031720246 cites W170428794 @default.
- W2031720246 cites W1964149678 @default.
- W2031720246 cites W1964261321 @default.
- W2031720246 cites W1967391569 @default.
- W2031720246 cites W1968323673 @default.
- W2031720246 cites W1971028883 @default.
- W2031720246 cites W1971253332 @default.
- W2031720246 cites W1981096579 @default.
- W2031720246 cites W1985103368 @default.
- W2031720246 cites W1999306810 @default.
- W2031720246 cites W2004759810 @default.
- W2031720246 cites W2015291446 @default.
- W2031720246 cites W2019093027 @default.
- W2031720246 cites W2019952415 @default.
- W2031720246 cites W2026055716 @default.
- W2031720246 cites W2027533965 @default.
- W2031720246 cites W2030033765 @default.
- W2031720246 cites W2032055715 @default.
- W2031720246 cites W2032235066 @default.
- W2031720246 cites W2032251372 @default.
- W2031720246 cites W2035951460 @default.
- W2031720246 cites W2039491462 @default.
- W2031720246 cites W2041313070 @default.
- W2031720246 cites W2044361162 @default.
- W2031720246 cites W2045166052 @default.
- W2031720246 cites W2047709368 @default.
- W2031720246 cites W2048263075 @default.
- W2031720246 cites W2054144845 @default.
- W2031720246 cites W2059037016 @default.
- W2031720246 cites W2067288654 @default.
- W2031720246 cites W2069881514 @default.
- W2031720246 cites W2071432029 @default.
- W2031720246 cites W2072495073 @default.
- W2031720246 cites W2079539653 @default.
- W2031720246 cites W2088013881 @default.
- W2031720246 cites W2091755560 @default.
- W2031720246 cites W2092263253 @default.
- W2031720246 cites W2098924026 @default.
- W2031720246 cites W2101201550 @default.
- W2031720246 cites W2106626264 @default.
- W2031720246 cites W2107826507 @default.
- W2031720246 cites W2109078622 @default.
- W2031720246 cites W2112641034 @default.
- W2031720246 cites W2112943515 @default.
- W2031720246 cites W2121876900 @default.
- W2031720246 cites W2132912591 @default.
- W2031720246 cites W2147476448 @default.
- W2031720246 cites W2151222524 @default.
- W2031720246 cites W2153757671 @default.
- W2031720246 cites W2329058421 @default.
- W2031720246 cites W2330922316 @default.
- W2031720246 cites W2443402937 @default.
- W2031720246 cites W4211075026 @default.
- W2031720246 doi "https://doi.org/10.1182/blood-2007-01-066076" @default.
- W2031720246 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17446348" @default.
- W2031720246 hasPublicationYear "2007" @default.
- W2031720246 type Work @default.
- W2031720246 sameAs 2031720246 @default.
- W2031720246 citedByCount "184" @default.
- W2031720246 countsByYear W20317202462012 @default.
- W2031720246 countsByYear W20317202462013 @default.
- W2031720246 countsByYear W20317202462014 @default.
- W2031720246 countsByYear W20317202462015 @default.
- W2031720246 countsByYear W20317202462016 @default.
- W2031720246 countsByYear W20317202462017 @default.
- W2031720246 countsByYear W20317202462018 @default.
- W2031720246 countsByYear W20317202462019 @default.
- W2031720246 countsByYear W20317202462020 @default.
- W2031720246 countsByYear W20317202462021 @default.
- W2031720246 countsByYear W20317202462022 @default.
- W2031720246 countsByYear W20317202462023 @default.