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The role of SRC family kinases in FLT3 signaling

Kazi, Julhash U. LU orcid and Rönnstrand, Lars LU orcid (2019) In International Journal of Biochemistry and Cell Biology 107. p.32-37
Abstract

The receptor tyrosine kinase FLT3 is expressed almost exclusively in the hematopoietic compartment. Binding of its ligand, FLT3 ligand (FL), induces dimerization and activation of its intrinsic tyrosine kinase activity. This leads to autophosphorylation of FLT3 on several tyrosine residues which constitute high affinity binding sites for signal transduction molecules. Recruitment of these signal transduction molecules to FLT3 leads to the activation of several signal transduction pathways that regulate cell survival, cell proliferation and differentiation. Oncogenic, constitutively active mutants of FLT3 are known to be expressed in acute myeloid leukemia and to correlate with poor prognosis. Activation of the receptor mediates cell... (More)

The receptor tyrosine kinase FLT3 is expressed almost exclusively in the hematopoietic compartment. Binding of its ligand, FLT3 ligand (FL), induces dimerization and activation of its intrinsic tyrosine kinase activity. This leads to autophosphorylation of FLT3 on several tyrosine residues which constitute high affinity binding sites for signal transduction molecules. Recruitment of these signal transduction molecules to FLT3 leads to the activation of several signal transduction pathways that regulate cell survival, cell proliferation and differentiation. Oncogenic, constitutively active mutants of FLT3 are known to be expressed in acute myeloid leukemia and to correlate with poor prognosis. Activation of the receptor mediates cell survival, cell proliferation and differentiation of cells. Several of the signal transduction pathways downstream of FLT3 have been shown to include various members of the SRC family of kinases (SFKs). They are involved in regulating the activity of RAS/ERK pathways through the scaffolding protein GAB2 and the adaptor protein SHC. They are also involved in negative regulation of signaling through phosphorylation of the ubiquitin E3 ligase CBL. Initially studied as the SFKs, as if they were a homogenous group of kinases, recent data suggest that each SFK has its own specific signaling capabilities where some are involved in positive signaling, while others are involved in negative signaling. This review discusses some recent insights into how SFKs are involved in FLT3 signaling.

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publication status
published
subject
keywords
Acute myeloid leukemia, FLT3, FLT3 ligand, Receptor tyrosine kinase, Src family kinase
in
International Journal of Biochemistry and Cell Biology
volume
107
pages
6 pages
publisher
Elsevier
external identifiers
  • pmid:30552988
  • scopus:85058403474
ISSN
1357-2725
DOI
10.1016/j.biocel.2018.12.007
language
English
LU publication?
yes
id
61dbb7f9-c9d1-4803-a6c7-3736cef81854
date added to LUP
2018-12-30 22:57:07
date last changed
2024-03-18 21:51:38
@article{61dbb7f9-c9d1-4803-a6c7-3736cef81854,
  abstract     = {{<p>The receptor tyrosine kinase FLT3 is expressed almost exclusively in the hematopoietic compartment. Binding of its ligand, FLT3 ligand (FL), induces dimerization and activation of its intrinsic tyrosine kinase activity. This leads to autophosphorylation of FLT3 on several tyrosine residues which constitute high affinity binding sites for signal transduction molecules. Recruitment of these signal transduction molecules to FLT3 leads to the activation of several signal transduction pathways that regulate cell survival, cell proliferation and differentiation. Oncogenic, constitutively active mutants of FLT3 are known to be expressed in acute myeloid leukemia and to correlate with poor prognosis. Activation of the receptor mediates cell survival, cell proliferation and differentiation of cells. Several of the signal transduction pathways downstream of FLT3 have been shown to include various members of the SRC family of kinases (SFKs). They are involved in regulating the activity of RAS/ERK pathways through the scaffolding protein GAB2 and the adaptor protein SHC. They are also involved in negative regulation of signaling through phosphorylation of the ubiquitin E3 ligase CBL. Initially studied as the SFKs, as if they were a homogenous group of kinases, recent data suggest that each SFK has its own specific signaling capabilities where some are involved in positive signaling, while others are involved in negative signaling. This review discusses some recent insights into how SFKs are involved in FLT3 signaling.</p>}},
  author       = {{Kazi, Julhash U. and Rönnstrand, Lars}},
  issn         = {{1357-2725}},
  keywords     = {{Acute myeloid leukemia; FLT3; FLT3 ligand; Receptor tyrosine kinase; Src family kinase}},
  language     = {{eng}},
  month        = {{02}},
  pages        = {{32--37}},
  publisher    = {{Elsevier}},
  series       = {{International Journal of Biochemistry and Cell Biology}},
  title        = {{The role of SRC family kinases in FLT3 signaling}},
  url          = {{http://dx.doi.org/10.1016/j.biocel.2018.12.007}},
  doi          = {{10.1016/j.biocel.2018.12.007}},
  volume       = {{107}},
  year         = {{2019}},
}