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

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

  • Cancer Cell. 2007 Sep;12(3):201-14. doi: 10.1016/j.ccr.2007.08.003.
Sumin Kang 1,  Shaozhong Dong,  Ting-Lei Gu,  Ailan Guo,  Michael S Cohen,  Sagar Lonial,  Hanna Jean Khoury,  Doriano Fabbro,  D Gary Gilliland,  P Leif Bergsagel,  Jack Taunton,  Roberto D Polakiewicz,  Jing Chen
Affiliations

Affiliation

  • 1 Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA.
PMID: 17785202 DOI: 10.1016/j.ccr.2007.08.003
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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