GEF guanine nucleotide exchange factors

DBS deep brain stimulation GEF guanine nucleotide exchange factor... 

Fig. 3 A AGS proteins isolated in yeast-based functional screen G-protein signaling modulator (GPSM) as named by the Human Genome Nomenclature Committee. The major sites of action of AGS proteins in the context of the G-protein activation-deactivation cycle are indicated B on the right. (GPR G-protein regulatory, GEF guanine nucleotide exchange factor, GDI guanine nucleotide dissociation inhibitor, GPCR G-protein coupled receptor)...

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.

Abbreviations GEF, guanine nucleotide exchange factor CBP, cap-binding protein. 

Guanine nucleotide exchange factors (GEFs) are proteins which catalyse the release of nucleotide bound to small GTPases. 

Vav proteins are guanine nucleotide exchange factors (GEF) for monomeric GTPases. Tire Vav proteins belong to the DBL family of Rho GEFs and have an important role in regulating early events in receptor signalling. 

The discovery of PLCs reveals a fourth mechanism whereby the enzyme can be activated (Fig. 20-5). PLCs possesses two Ras-binding (RA) domains in its carboxyl terminal region, and occupancy of these by Ras-GTP results in activation of the enzyme. In addition, the enzyme possesses a CDC-25 domain at its N-terminus, which serves as a guanine nucleotide exchange factor (GEF) for small GTP-binding proteins such as Ras or RaplA. Thus PLCe can not only activate the GDP-bound forms of these small GTP-binding proteins but can also be... 

Figure 21.7 Control of the activity of Ras by a balance of the activities of guanine nucleotide exchange factor and GTPase. GAP is the abbreviation for GTPase-activating factor and GEF for guanine nucleotide exchange factor. Both are enzymes. Both the activities are controlled by stimuli from various cell surface receptors. Ras oncogenes are present in about 30% of all human tumours.

Acceleration of the dissociation of GDP increases the proportion of the active form. The rate of dissociation of GDP may be increased by specific proteins. These proteins are known as guanine nucleotide exchange factors (GEF). For the heterotrimeric G-proteins, the agonist-boimd, activated receptor is the exchange factor. 

The transition from inactive GDP state to active GTP state may be accelerated by proteins that cause the boimd GDP to dissociate. The guanine nucleotide exchange factors (GEF) play an essential role in signal transduction via Ras proteins. Loss of exchange activity by mutation of the exchange proteins has the same effect in lower organisms as loss of the Ras gene. 

Fig. 9.2. The GTPase cycle of the Ras protein. Conversion of the inactive Ras GDP complex into the active Ras GTP complex is brought about by guanine nucleotide exchange factors (GEFs). The activated state of the Ras protein is terminated by hydrolysis of the bound GTP. The help of a GTPase actvating protein (GAP) is required, due to the intrinsically slow GTPase activity of the Ras protein. Ras protein performs all its functions in close association with the cell membrane. It carries a membrane anchor and the effector proteins preceding and following in sequence are also associated with the membrane.

Guanine Nucleotide Exchange Factors (GEFs) in Signal Transduction via Ras Proteins... 

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