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Emory researchers identify signaling protein for multiple myeloma
Date:9/10/2007

myeloma cells. This means FGFR3 requires RSK2 to transform normal cells.

This is a beautiful model, says Dr. Chen. We are able to mark the connection between the oncogenic FGFR3 and its downstream protein kinase RSK2, which plays a critical role in regulation of cell cycle and survival. These findings extend our understanding of pathogenesis of multiple myeloma in a signaling basis.

Collaborators on the project include Roberto Polakiewicz, PhD, and Ting-Lei Gu, PhD, both of Cell Signaling Technologies (CST), developers of the PhosphoScan technology, which enables investigators to identify hundreds to thousands of phosphorylated sequences and observe the global state of protein tyrosine phosphorylation in cells and tissues.

Using this technology, says Dr. Chen, we identified RSK2 as a critical downstream signaling protein effector of FGFR3 in myeloma cells. Other authors include researchers from the University of California at San Francisco, Harvard Medical School, Mayo Clinic and Novartis Pharma AG.

Dr. Chen and his colleagues also tested a drug called fmk that was designed by co-author Jack Taunton, PhD, at UCSF to specifically target RSK2 in treatment of human malignant myeloma cells from laboratory culture or primary samples from multiple myeloma patients, and saw that fmk effectively kills t(4;14) myeloma cells with abnormal over-expression of FGFR3.

This study shows the potential utility of drugs that block the downstream effectors of mutant tyrosine kinases, and that these drugs are opening more doors to treating hematologic malignancies and cancers," explains Dr. Chen. In addition to the t(4;14) in multiple myeloma that is caused by abnormal over-expression of FGFR3, abnormality of FGFR3 has also been identified in human bladder and cervical cancers. The findings suggest, the authors write, that targeting RSK2 with RSK inhibitors such as fmk may be effective in treating t(4;14) multiple myeloma, as well as oth
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Contact: Vincent Dollard
vincent.dollard@emoryhealthcare.org
404-778-4580
Emory University
Source:Eurekalert

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