Ubiquitination of FLT3

Stable Identifier
R-HSA-9706354
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
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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
19276253 CBL exon 8/9 mutants activate the FLT3 pathway and cluster in core binding factor/11q deletion acute myeloid leukemia/myelodysplastic syndrome subtypes

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

Clin Cancer Res 2009
31066629 FMS-like Tyrosine Kinase 3/FLT3: From Basic Science to Clinical Implications

Kazi, JU, Rönnstrand, L

Physiol. Rev. 2019
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

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

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

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

Blood 2007
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
ubiquitin protein ligase activity of FLT3 E3 ubiquitin ligases [plasma membrane]
Physical Entity
Activity
Orthologous Events
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Created
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