FLT3 signaling through SRC family kinases

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Homo sapiens
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Several SRC family kinases (SFKs) have been shown to interact with active FLT3 to modulate downstream signaling. These include FYN, HCK, LCK and SYK (Heiss et al, 2006; Mitina et al, 2007; Chougule et al, 2016; Dosil et al, 1993; Marhall et al, 2017; Puissant et al, 2014; reviewed in Kazi and Ronnstrand, 2019a,b). The role of SFKs downstream of FLT3 is complex and not fully elucidated. Some family members appear to contribute positively to signaling, as assessed by elevated STAT5 signaling, while others may contribute to ubiquitin ligation and downregulation of the receptor through interaction with CBL (Chougule et al, 2016; Heiss et al, 2006; Marhall et al, 2017; reviewed in Kazi and Ronnstrand, 2019a,b).

Literature References
PubMed ID Title Journal Year
7692230 Mitogenic signalling and substrate specificity of the Flk2/Flt3 receptor tyrosine kinase in fibroblasts and interleukin 3-dependent hematopoietic cells

Wang, S, Dosil, M, Lemischka, IR

Mol. Cell. Biol. 1993
30552988 The role of SRC family kinases in FLT3 signaling

Kazi, JU, Rönnstrand, L

Int. J. Biochem. Cell Biol. 2019
26848862 FYN expression potentiates FLT3-ITD induced STAT5 signaling in acute myeloid leukemia

Kazi, JU, Chougule, RA, Rönnstrand, L

Oncotarget 2016
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
24525236 SYK is a critical regulator of FLT3 in acute myeloid leukemia

Hemann, MT, Galinsky, I, Luciano, F, Stegmaier, K, Kazi, JU, Kung, AL, Bassil, CF, Mehta, S, Pikman, Y, Fenouille, N, Stone, RM, Alexe, G, Puissant, A, Aster, JC, Deangelo, DJ, Rönnstrand, L, Du, J

Cancer Cell 2014
29062038 The Src family kinase LCK cooperates with oncogenic FLT3/ITD in cellular transformation

Kazi, JU, Rönnstrand, L, Marhäll, A

Sci Rep 2017
17668209 Src family tyrosine kinases phosphorylate Flt3 on juxtamembrane tyrosines and interfere with receptor maturation in a kinase-dependent manner

Krause, G, Hallek, M, Mitina, O, Warmuth, M, Obermeier, A

Ann. Hematol. 2007
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