1. Model for regulation of the Ras p21 product and for the GTPase-activating protein (GAP) as a downstream effector and regulator of ras activity. Ras is localized to the inner aspect of the plasma membrane. The alternating relaxed (GDP bound) and activated (GTP bound) states of the p21 Ras protein are shown in normal cells. Conversion of GDP- to GTP-bound forms is the rate-limiting step. Binding of the Grb2 adaptor protein to a specific tyrosine-phosphorylated residue on an activated (growth factor stimulated) receptor tyrosine kinase translocates the Sos guanine nucleotide exchange factor to the plasma membrane, where it stimulates the exchange of GDP for GTP on Ras. Activation of Ras alters its conformation and enables it to interact with and recruit the Raf serine-threonine kinase to the membrane where it becomes activated by an unknown (not Ras) mechanism. Activation of Raf activates the downstream MAP kinase signaling pathway involved in the mitogenic response. In addition, activation of Ras stimulates changes in cell shape and motility mediated through Rho-like GTPase proteins that are part of the Ras superfamily of small GTPase proteins. Inactivation of Ras is in part controlled by the intrinsic intrinsic Ras GTPase, catalyzed by GTPase-activating proteins (GAP and NF1). Oncogenic p21 Ras proteins with mutations at amino acid positions 12, 13, 59, or 61 remain in their active GTP-bound states and constitutively activate downstream signaling pathways.
Source: Oncogenes, The Online Metabolic and Molecular Bases of Inherited Disease
Citation: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G. The Online Metabolic and Molecular Bases of Inherited Disease; 2014 Available at: Accessed: October 08, 2017
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