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Grb2 holds powerful molecular signaling pathway in check
Date:6/22/2012

Their findings provide a possible mechanism to explain why genomic deletions found in bladder and gastric cancer and point mutations in melanoma might promote those cancers.

In each case, the portion of the gene that encodes FGFR's internal signaling domain is affected. If that domain is abnormal, Grb2 would not be able to bind it."That could lead to the FGFR pathway being turned on constantly," Ladbury said.

FGFR launches the MAPK signaling pathway, which is known to promote cancer when abnormally activated. Ladbury and colleagues have identified a potential tumor-suppressing role for Grb2.

The team developed and confirmed the relationship between Grb2 and FGFR via cell biology experiments, biophysics and structural analysis."I'm extremely proud of this group, which can cover all of those bases and provide a full explanation of a system," Ladbury noted.

The Ladbury group continues to investigate:

  • Whether cancer cells are predisposed to have abnormal levels of Grb2 , which would affect the control of FGFR signaling.

  • How disruption of the cycle of Grb2 binding and release leads to cancer.

  • The mechanism by which Grb2 is phosphorylated by FGFR.


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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert  

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