Question

Which of the following alterations to the signaling pathway would lead to increased transcription by the CREB protein?

1) inhibition of adenylyl cyclase
2) inhibition of entry of PKA into the nucleus
3) inhibition of GTP hydrolysis
4) inhibition of cAMP breakdown

Answer 1

To increase transcription by the CREB protein, inhibition of cAMP breakdown is the option that would lead to such an outcome. This is because cAMP activates PKA, which then phosphorylates and activates . option 4 is correct answer.

Step-by-step explanation:

To increase transcription by the CREB protein, it is necessary to enhance the signaling pathway that activates CREB. Among the given options, the one that leads to increased transcription by the CREB protein is inhibition of cAMP breakdown.

In the G-protein signaling pathway, the activation of adenylyl cyclase leads to the production of cAMP, which in turn activates Protein Kinase A (PKA). Once activated, PKA enters the nucleus and phosphorylates the CREB protein, which initiates transcription. Therefore, inhibiting the breakdown of cAMP by phosphodiesterase (PDE), which normally functions to control hormone activity, would increase the amount of cAMP available to activate PKA and, subsequently, CREB.

Inhibition of adenylyl cyclase or inhibition of PKA's entry into the nucleus would lead to a decrease in CREB-mediated transcription. Moreover, inhibition of GTP hydrolysis would generally increase signaling, but this is not directly related to CREB's activation, which specifically requires the activity of PKA inside the nucleus.