30. In cells having G protein coupled receptor, inhibition of protein kinase A by siRNA technology led to diminished transcription of androgen binding protein (ABP) and CREB protein. Addition of cAMP, which is a second messenger, will lead to
(1) increased transcription of ABP.
(2) increased phosphorylation of CREB protein.
(3) no change in transcription level.
(4) increased ATPase activity of G_α subunit.

 

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Introduction

In cells with G protein-coupled receptors (GPCRs), the second messenger cyclic AMP (cAMP) plays a pivotal role in signal transduction. It primarily functions by activating protein kinase A (PKA), which then phosphorylates key transcription factors like CREB (cAMP response element-binding protein), leading to altered gene expression.

Background

In the described scenario, inhibition of PKA via siRNA leads to diminished transcription of androgen binding protein (ABP) and CREB proteins—signaling a direct regulatory role of PKA in this transcriptional activity.

Adding cAMP, which activates PKA, could potentially restore or enhance phosphorylation and transcriptional activity unless PKA levels remain insufficient.

What Happens Upon Addition of cAMP?

• PKA Activation: cAMP binds to the regulatory subunits of PKA holoenzyme, releasing the catalytic subunits.

• CREB Phosphorylation: Activated PKA phosphorylates CREB, which then binds to DNA elements promoting gene transcription.

• ABP Transcription: Since ABP transcription is regulated by PKA-CREB signaling, increased CREB phosphorylation promotes ABP gene expression.

Evaluating the Options

1. Increased transcription of ABP: Likely if PKA is sufficiently reactivated by cAMP.

2. Increased phosphorylation of CREB protein: Direct effect of activated PKA through cAMP binding.

3. No change in transcription level: Unlikely, as cAMP’s effect strongly influences transcription via PKA.

4. Increased ATPase activity of Gα subunit: Irrelevant, as cAMP primarily affects PKA and downstream transcription.

Most Accurate Outcome

Option (2) increased phosphorylation of CREB protein is the immediate direct effect of cAMP addition. Increased CREB phosphorylation precedes and drives transcriptional changes such as ABP expression.

While (1) increased ABP transcription will occur downstream, (2) is the more direct and immediate measurable biochemical event following cAMP addition.

Conclusion

Adding cAMP in cells where PKA is inhibited leads primarily to increased phosphorylation of CREB protein (Option 2), which subsequently enhances transcription of genes like ABP.