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- Title
Indirubin-3′-monoxime inhibits autophosphorylation of FGFR1 and stimulates ERK1/2 activity via p38 MAPK.
- Authors
Zhen, Y.; Sørensen, V.; Jin, Y.; Suo, Z.; Więdłocha, A.
- Abstract
Indirubin-3′-monoxime is a derivative of the bis-indole alkaloid indirubin, an active ingredient of a traditional Chinese medical preparation that exhibits anti-inflammatory and anti-leukemic activities. Indirubin-3′-monoxime is mainly recognized as an inhibitor of cyclin-dependent kinases (CDKs) and glycogen synthase kinase-3. It inhibits proliferation of cultured cells, mainly through arresting the cells in the G1/S or G2/M phase of the cell cycle. Here, we report that indirubin-3′-monoxime is able to inhibit proliferation of NIH/3T3 cells by specifically inhibiting autophosphorylation of fibroblast growth factor receptor 1 (FGFR1), blocking in this way the receptor-mediated cell signaling. Indirubin-3′-monoxime inhibits the activity of FGFR1 at a concentration lower than that required for inhibition of phosphorylation of CDK2 and retinoblastoma protein and cell proliferation stimulated by fetal calf serum. The ability of indirubin-3′-monoxime to inhibit FGFR1 signaling was similar to that of the FGFR1 inhibitor SU5402. In addition, we found that indirubin-3′-monoxime activates long-term p38 mitogen-activated protein kinase activity, which stimulates extracellular signal-regulated kinase 1/2 in a way unrelated to the activity of FGFR1. Furthermore, we show that indirubin-3′-monoxime can inhibit proliferation of the myeloid leukemia cell line KG-1a through inhibition of the activity of the FGFR1 tyrosine kinase. The data presented here demonstrate previously unknown activities of indirubin-3′-monoxime that may have clinical implications.Oncogene (2007) 26, 6372–6385; doi:10.1038/sj.onc.1210473; published online 28 May 2007
- Subjects
INDIRUBIN; PHOSPHORYLATION; CYCLIN-dependent kinases; PROTEIN kinases; FIBROBLAST growth factors; ONCOGENES; CANCER genes
- Publication
Oncogene, 2007, Vol 26, Issue 44, p6372
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1210473