Advanced

Suppressor of cytokine signaling 2 (SOCS2) associates with FLT3 and negatively regulates downstream signaling.

Kazi, Julhash U. LU and Rönnstrand, Lars LU (2013) In Molecular Oncology 7(3). p.693-703
Abstract
The suppressor of cytokine signaling 2 (SOCS2) is a member of the SOCS family of E3 ubiquitin ligases. SOCS2 is known to regulate signal transduction by cytokine receptors and receptor tyrosine kinases. The receptor tyrosine kinase FLT3 is of importance for proliferation, survival and differentiation of hematopoietic cells and is frequently mutated in acute myeloid leukemia. We observed that SOCS2 associates with activated FLT3 through phosphotyrosine residues 589 and 919, and co-localizes with FLT3 in the cell membrane. SOCS2 increases FLT3 ubiquitination and accelerates receptor degradation in proteasomes. SOCS2 negatively regulates FLT3 signaling by blocking activation of Erk 1/2 and STAT5. Furthermore, SOCS2 expression leads to a... (More)
The suppressor of cytokine signaling 2 (SOCS2) is a member of the SOCS family of E3 ubiquitin ligases. SOCS2 is known to regulate signal transduction by cytokine receptors and receptor tyrosine kinases. The receptor tyrosine kinase FLT3 is of importance for proliferation, survival and differentiation of hematopoietic cells and is frequently mutated in acute myeloid leukemia. We observed that SOCS2 associates with activated FLT3 through phosphotyrosine residues 589 and 919, and co-localizes with FLT3 in the cell membrane. SOCS2 increases FLT3 ubiquitination and accelerates receptor degradation in proteasomes. SOCS2 negatively regulates FLT3 signaling by blocking activation of Erk 1/2 and STAT5. Furthermore, SOCS2 expression leads to a decrease in FLT3-ITD-mediated cell proliferation and colony formation. Thus, we suggest that SOCS2 associates with activated FLT3 and negatively regulates the FLT3 signaling pathways. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Oncology
volume
7
issue
3
pages
693 - 703
publisher
Elsevier
external identifiers
  • wos:000321233400032
  • pmid:23548639
  • scopus:84878110355
ISSN
1574-7891
DOI
10.1016/j.molonc.2013.02.020
language
English
LU publication?
yes
id
c7015283-9740-4713-b623-658640aa44a9 (old id 3734284)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23548639?dopt=Abstract
date added to LUP
2013-05-02 10:11:53
date last changed
2018-11-21 19:47:36
@article{c7015283-9740-4713-b623-658640aa44a9,
  abstract     = {The suppressor of cytokine signaling 2 (SOCS2) is a member of the SOCS family of E3 ubiquitin ligases. SOCS2 is known to regulate signal transduction by cytokine receptors and receptor tyrosine kinases. The receptor tyrosine kinase FLT3 is of importance for proliferation, survival and differentiation of hematopoietic cells and is frequently mutated in acute myeloid leukemia. We observed that SOCS2 associates with activated FLT3 through phosphotyrosine residues 589 and 919, and co-localizes with FLT3 in the cell membrane. SOCS2 increases FLT3 ubiquitination and accelerates receptor degradation in proteasomes. SOCS2 negatively regulates FLT3 signaling by blocking activation of Erk 1/2 and STAT5. Furthermore, SOCS2 expression leads to a decrease in FLT3-ITD-mediated cell proliferation and colony formation. Thus, we suggest that SOCS2 associates with activated FLT3 and negatively regulates the FLT3 signaling pathways.},
  author       = {Kazi, Julhash U. and Rönnstrand, Lars},
  issn         = {1574-7891},
  language     = {eng},
  number       = {3},
  pages        = {693--703},
  publisher    = {Elsevier},
  series       = {Molecular Oncology},
  title        = {Suppressor of cytokine signaling 2 (SOCS2) associates with FLT3 and negatively regulates downstream signaling.},
  url          = {http://dx.doi.org/10.1016/j.molonc.2013.02.020},
  volume       = {7},
  year         = {2013},
}