The cycling of monomeric G proteins, such as Ras, between active and inactive states is aided by accessory proteins that bind to the G protein and regulate its activity. These accessory proteins include GTPase-activating proteins (GAPs) and guanine nucleotide-exchange factors (GEFs). The following conditions refer to different states of GAP and GEF proteins:

A. A non-functional GAP
B. A permanently activated GAP
C. A non-functional GEF
D. A permanently activated GEF

Which one of the following options represents conditions/states that might cause a constantly activated signaling cascade?

Correct option is D

The GTPase cycle of monomeric G proteins (like Ras) is tightly regulated by two key proteins:

1. GTPase-activating proteins (GAPs):

   • These inactivate G proteins by stimulating their intrinsic GTPase activity, converting GTP to GDP.
   • A non-functional GAP (A) means Ras remains in the active GTP-bound state, leading to constant signaling.

2. Guanine nucleotide exchange factors (GEFs):

   • These activate G proteins by promoting the exchange of GDP for GTP, switching Ras to its active form.
   • A permanently activated GEF (D) means continuous GTP loading on Ras, keeping it constantly active.

Analysis of the Statements:

1. A - A non-functional GAP (Correct )

   • Since GAPs are responsible for turning off G proteins, a non-functional GAP means GTP-bound Ras cannot be inactivated, leading to constant signaling.

2. B - A permanently activated GAP (Incorrect )

   • If GAP is overactive, it will continuously turn off Ras, leading to reduced signaling, not activation.

3. C - A non-functional GEF (Incorrect )

   • If GEF is non-functional, GDP cannot be exchanged for GTP, leading to decreased Ras activation, not a constantly activated cascade.

4. D - A permanently activated GEF (Correct )

   • If GEF is overactive, it will constantly exchange GDP for GTP, keeping Ras in the active state and leading to continuous signaling.