Guanine activating proteins

Figure 6.4. Mode of action of low-molecular-weight G-proteins. The raslike proteins normally bind GDP, but this may be exchanged for GTP via a process that may be assisted by guanine nucleotide exchange protein (GNEP). The GTP-bound ras protein may then interact with and activate its target protein (X). The activity of GTPase activating protein (GAP) may then assist to hydrolyse GTP to GDP, to inhibit ras activity.

These GTPases cycle between inactive GDP-bound forms and active GTP-bound forms. Eukaryotic-specific domain families have evolved that either promote GTPase activities (GTPase activator proteins, GAPs ) or promote exchange of GDP for GTP (guanine nucleotide exchange... 

Fig. 9.1. The Ras protein as a central switching station of signaling pathways. A main pathway for Ras activation is via receptor tyrosine kinases, which pass the signal on via adaptor proteins and guanine nucleotide exchange factors to the Ras protein. Activation ofRas protein can also be initiated via G-protein-coupled receptors and via transmembrane receptors with associated tyrosine kinase activity. The membrane association of the Ras protein (see Fig. 9.6) is not shown for clarity. In addition, not aU signahng pathways that contribute to activation of the Ras protein are shown, nor are all effector reactions. Py omplex of the heterotrimeric G proteins GAP GTPase activating protein GEF guanine nucleotide exchange factor.

The SOS guanine-nucleotide exchange factor mediates GTP loading of Ras (Fig. 2), leading to activation of evolutionarily conserved effector proteins, such as the Raf ser-ine/threonine kinase, P13 K, and Ral-GDS. Raf activation triggers a cascade of phosphorylation events that lead to mitogen-activated protein kinase (MAPK) activation. 

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