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Ras and related proteins of the Ras superfamily play critical roles in the control of normal and neoplastic proliferation. In mammalian cells there are four true Ras proteins (encoded by Ha- ras , N- ras , Ki- ras A, and Ki- ras B ) which, upon mutational activation, can function as independent oncogenes. These proteins relay signals from tyrosine kinases at the plasma membrane which subsequently lead to the nucleus via a network of serine/threonine kinases . The p21ras protein is active in its GTP-bound state. This form is slowly converted to the GDP-bound form by the intrinsic GTPase activity of Ras. This activity is greatly enhanced byGTPase-activating proteins (GAPs) which subsequently lead to removal of the GTP molecule and replacement with GDP. Maintenance of Ras in the GTP form can lead to transformation. One class of Ras mutations, commonly found in human tumors, results in an accumulation of Ras-GTP. The mutant Ras can bind GAP, but GAP bound in this manner seems unable to affect the Ras-GTPase activity.
