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Mol Oncol. 2013 Jun;7(3):693-703. doi: 10.1016/j.molonc.2013.02.020. Epub 2013 Mar 19.

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

Author information

1
Experimental Clinical Chemistry, Department of Laboratory Medicine, Lund University, Wallenberg Laboratory, Skåne University Hospital, 20502 Malmö, Sweden.

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.

PMID:
23548639
PMCID:
PMC5528470
DOI:
10.1016/j.molonc.2013.02.020
[Indexed for MEDLINE]
Free PMC Article

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