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New Study Reveals the Complexity of RAS Signaling in the Brain


Recent work by Dr. R. Hugh Bender, a former PhD graduate student in Dr. David Gutmann’s laboratory, demonstrated that the consequence of RAS activation may be more complex than previously appreciated. One of the major functions of the Neurofibromatosis type 1 (NF1) protein, called neurofibromin, is to convert RAS from an active to an inactive form. RAS, when active, increases cell growth. However, in brain cells, there are three distinct types of RAS, which each could operate differently to control cell growth.

Using a series of mouse strains engineered to express activated versions of each of these three RAS proteins, Dr. Bender showed that only one RAS molecule, called Kirsten-RAS (K-RAS) caused brain progenitor cells to grow faster. Moreover, he found that this particular RAS molecule increases progenitor cell growth by controlling the activity of the retinoblastoma (RB) protein, rather than by signaling through more commonly known molecules, like RAF or AKT.

Based on these studies, scientists must consider which RAS is activated in tumors from people with NF1, and to design treatments that most effectively block the responsible RAS protein.

Bender RH, Haigis KM, Gutmann DH. Activated K-Ras, but not H-Ras or N-Ras, regulates brain neural stem cell proliferation in a Raf/Rb-dependent manner. STEM CELLS. 2015; doi: 10.1002/stem.1990.