Ubiquitination of FLT3

Stable Identifier
Reaction [omitted]
Homo sapiens
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FLT3 activity is negatively regulated by ubiquitin-mediated internalization (Sargin et al, 2007; Reindl et al, 2009; reviewed in Kazi and Ronnstrand, 2019). Several E3 ubiquitin ligases are implicated in the downregulation of active FLT3 including CBL, SOCS2 and SOCS6 (Sargin et al, 2007, Reindl et al, 2009; Kazi and Ronnstrand, 2013; Kazi et al, 2012).
Ubiquitination of human FLT3 in COS-7 cells is abrogated by the expression of a dominant negative form of CBL, implicating CBL as a major E3 ubiquitin ligase for the FLT3 receptor (Sargin et al, 2007). While direct ubiquitination of FLT3 by SOCS2 and SOCS6 has not been demonstrated, overexpression of these E3 ligases induces FLT3 ubiquitination and internalization in cell lines (Kazi and Ronnstrand, 2012; Kazi and Ronnstrand, 2013; reviewed in Kazi and Ronnstrand, 2019).
Literature References
PubMed ID Title Journal Year
31066629 FMS-like Tyrosine Kinase 3/FLT3: From Basic Science to Clinical Implications

Kazi, JU, Rönnstrand, L

Physiol. Rev. 2019
19276253 CBL exon 8/9 mutants activate the FLT3 pathway and cluster in core binding factor/11q deletion acute myeloid leukemia/myelodysplastic syndrome subtypes

Buske, C, Duyster, J, Reindl, C, Spiekermann, K, Vempati, S, Bohlander, SK, Humphries, KR, Greif, PA, Mellert, G, Argiropoulos, B, Hiddemann, W, Quentmeier, H, Benthaus, T, Petropoulos, K

Clin Cancer Res 2009
23548639 Suppressor of cytokine signaling 2 (SOCS2) associates with FLT3 and negatively regulates downstream signaling

Kazi, JU, Rönnstrand, L

Mol Oncol 2013
22952242 Suppressor of cytokine signaling 6 (SOCS6) negatively regulates Flt3 signal transduction through direct binding to phosphorylated tyrosines 591 and 919 of Flt3

Flores-Morales, A, Kazi, JU, Sun, J, Zadjali, F, Phung, B, Rönnstrand, L

J Biol Chem 2012
17446348 Flt3-dependent transformation by inactivating c-Cbl mutations in AML

Berdel, WE, Grundler, R, Serve, H, Duyster, J, Brandts, C, Tickenbrock, L, Choudhary, C, Koschmieder, S, Dikic, I, Müller-Tidow, C, Schwäble, J, August, B, Thiessen, C, Crosetto, N, Sargin, B, Rensinghoff, M, Bandi, SR, Schmidt, MHH

Blood 2007
Catalyst Activity

ubiquitin protein ligase activity of FLT3 E3 ubiquitin ligases [plasma membrane]

Orthologous Events
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