BMB Reports 2017; 50(7): 355-360
Structure, signaling and the drug discovery of the Ras oncogene protein
Chang Woo Han, Mi Suk Jeong & Se Bok Jang*
Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 46241, Korea
Correspondence to: Tel: +82-51-510-2523; Fax: +82-51-581-2544; E-mail:
Received: April 13, 2017; Revised: May 9, 2017; Accepted: May 28, 2017; Published online: July 31, 2017.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

Mutations in Ras GTPase are among the most common genetic alterations in human cancers. Despite extensive research investigating Ras proteins, their functions still remain a challenge over a long period of time. The currently available data suggests that solving the outstanding issues regarding Ras could lead to development of effective drugs that could have a significant impact on cancer treatment. Developing a better understanding of their biochemical properties or modes of action, along with improvements in their pharmacologic profiles, clinical design and scheduling will enable the development of more effective therapies.

Inhibitor, Mutation, Ras, Signaling

Fig. 2. Regulating signaling downstream of Ras. In the active GTP-bound state, Ras interacts with several families of effector proteins,
resulting in stimulation of their catalytic activities. Raf protein kinases activate mitogen-activated protein kinase kinases 1 and 2 (MEK1 and MEK2), which leads to ERK1/2 activation. Phosphoinositide 3-kinases (PI3Ks) generate second-messenger lipids and activate numerous target proteins, including the survival signaling kinase AkT/PDK1. Ras binding activates Ral specific guanine-nucleotide-exchange factors (Ral-GEFs) by targeting them to their substrates, Ral GTPases, which are present in the plasma membrane. Phospholipase Cε (PLCε) catalyses the activation of protein kinase C (PKC) and mobilization of calcium from intracellular stores.

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