Reactome | FLT3 signaling through SRC family kinases

FLT3 signaling through SRC family kinases

Stable Identifier

R-HSA-9706374

Type

Pathway

Species

Homo sapiens

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FLT3 signaling through SRC family kinases

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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
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
30552988	The role of SRC family kinases in FLT3 signaling Kazi, JU, Rönnstrand, L	Int. J. Biochem. Cell Biol.	2019
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
31066629	FMS-like Tyrosine Kinase 3/FLT3: From Basic Science to Clinical Implications Kazi, JU, Rönnstrand, L	Physiol. Rev.	2019
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
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
26848862	FYN expression potentiates FLT3-ITD induced STAT5 signaling in acute myeloid leukemia Kazi, JU, Chougule, RA, Rönnstrand, L	Oncotarget	2016