Reactome | Active FLT3 binds to CBL

Active FLT3 binds to CBL

Stable Identifier

R-HSA-9706293

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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Active FLT3 is bound by the E3 ubiquitin protein ligase CBL. In addition to direct interaction with the FLT3 receptor, CBL may also interact indirectly through GRB2. CBL interacts with the receptor in a FL ligand-dependent way, and mutation of FLT3 tyrosine residues Y589 and Y599 abrogates FLT3-dependent CBL phosphorylation (Sargin et al, 2007; Reindl et al, 2009; Heiss et al, 2006). FLT3-mediated phosphorylation of CBL promotes receptor ubiquitination and internalization, consistent with what is observed with other Type III receptor tyrosine kinases (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
16684964	Identification of Y589 and Y599 in the juxtamembrane domain of Flt3 as ligand-induced autophosphorylation sites involved in binding of Src family kinases and the protein tyrosine phosphatase SHP2 Masson, K, Sun, J, Bengtsson, S, Pedersen, M, Heiss, E, Sundberg, C, Rönnstrand, L	Blood	2006
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
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