FMS-like tyrosine kinase 3 interacts with the glucocorticoid receptor complex and affects glucocorticoid dependent signaling.
The glucocorticoid receptor (GR) forms part of a multiprotein complex consisting of chaperones and proteins active in glucocorticoid signaling and other pathways. By immunoaffinity purification of GR, followed by Edman sequencing and Western blotting, we identified the FMS-like tyrosine kinase 3 (Flt3) as a GR-interacting protein in rat liver and hepatoma cells. Flt3 interacts with both non-liganded and liganded GR. The DNA-binding domain of GR is sufficient for Flt3 interaction as shown by GST-pull down experiments. Studies of the effects of Flt3 and its ligand FL in glucocorticoid-driven reporter-gene assays in Cos7 cells, show that co-transfection with Flt3 and FL potentiates glucocorticoid effects. Treatment with FL had no effect on GR location and Dex induced translocation of GR was unaffected by FL. In summary, GR and Flt3 interact, affecting GR signaling. This novel cross-talk between GR and a hematopoietic growth factor might also imply glucocorticoid effects on Flt3-mediated signaling.
Asadi
Abolfazl
A
Department of Biosciences and Nutrition, Division of Medical Nutrition, Karolinska Institutet, NOVUM, S-141 86 Stockholm, Sweden.
Hedman
Erik
E
Widén
Christina
C
Zilliacus
Johanna
J
Gustafsson
Jan-Ake
JA
Wikström
Ann-Charlotte
AC
D000818:Animals; D002478:Cells, Cultured; D005938:Glucocorticoids / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D051941:fms-Like Tyrosine Kinase 3 / Q000378:metabolism*
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D051941:fms-Like Tyrosine Kinase 3