Guanine nucleotide exchange factors GEFs

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... 

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... 

---