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Cancer Cell. 2007 Sep;12(3):201-14.

FGFR3 activates RSK2 to mediate hematopoietic transformation through tyrosine phosphorylation of RSK2 and activation of the MEK/ERK pathway.

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  • 1Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA.

Abstract

To better understand the signaling properties of oncogenic FGFR3, we performed phospho-proteomics studies to identify potential downstream signaling effectors that are tyrosine phosphorylated in hematopoietic cells expressing constitutively activated leukemogenic FGFR3 mutants. We found that FGFR3 directly tyrosine phosphorylates the serine/threonine kinase p90RSK2 at Y529, which consequently regulates RSK2 activation by facilitating inactive ERK binding to RSK2 that is required for ERK-dependent phosphorylation and activation of RSK2. Moreover, inhibition of RSK2 by siRNA or a specific RSK inhibitor fmk effectively induced apoptosis in FGFR3-expressing human t(4;14)-positive myeloma cells. Our findings suggest that FGFR3 mediates hematopoietic transformation by activating RSK2 in a two-step fashion, promoting both the ERK-RSK2 interaction and subsequent phosphorylation of RSK2 by ERK.

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PMID:
17785202
[PubMed - indexed for MEDLINE]
PMCID:
PMC2424114
Free PMC Article
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