Question

You are interested in further understanding the signal transduction pathway that controls the production of Pig1, a protein important for regulating cell size. Activation of the TRK receptor leads to activation of the GTP-binding protein, Ras, which then activates a protein kinase that phosphorylates the SZE transcription factor. SZE only interacts with the nuclear transport receptor when it is phosphorylated. SZE is a gene activator for the Pig1 gene. This pathway is diagrammed in Figure Q16-50.Normal cells grown under standard conditions (without ligand) are 14 μm in diameter while normal cells exposed to TRK ligand are 10.5 μm in diameter. Given this situation, which of the following conditions do you predict will more likely lead to smaller cells?

(a) addition of TRK ligand and a drug that stimulates the GTPase activity of Ras
(b) addition of TRK ligand and a drug that inhibits the activity of the phosphatase that acts on SZE
(c) addition of TRK ligand and a drug that stimulates the degradation of Pig1
(d) addition of TRK ligand and a drug that inhibits Pig1 binding to DNA

Answer 1

The condition most likely leading to smaller cells would be the addition of TRK ligand along with a drug that inhibits the phosphatase that acts on the SZE transcription factor, as it would enhance Pig1 production. the most likely condition to create smaller cells would be (b) addition of TRK ligand and a drug that inhibits the activity of the phosphatase that acts on SZE, since this would enhance the activity of the signaling pathway that leads to Pig1 production, which is known to regulate cell size.

Step-by-step explanation:

In the signal transduction pathway described, the goal is to understand how the production of Pig1, a protein that regulates cell size, is controlled. Based on the pathway, TRK ligand binding to a receptor leads to a series of events that result in the production of Pig1 via the SZE transcription factor. When TRK is active, it activates Ras, which in turn activates a kinase. This kinase phosphorylates SZE, which can now enter the nucleus with the help of a nuclear transport receptor. Once inside, SZE can activate the Pig1 gene.

Considering the different conditions provided:

1. Addition of TRK ligand and a drug that stimulates the GTPase activity of Ras - This would most likely lead to inactivation of Ras and thus fewer smaller cells since the downstream effects on Pig1 production would be reduced.
2. Addition of TRK ligand and a drug that inhibits the activity of the phosphatase that acts on SZE - This would likely lead to more phosphorylation of SZE, and therefore, more production of Pig1, which could lead to smaller cells as the pathway is more active and the negative regulation is inhibited.
3. Addition of TRK ligand and a drug that stimulates the degradation of Pig1 - This would likely lead to larger cells, as the active Pig1 would be degraded and thus would not contribute to the regulation of cell size.
4. Addition of TRK ligand and a drug that inhibits Pig1 binding to DNA - This would prevent Pig1 from exerting its effects, likely leading to the production of larger cells as the gene regulation is impeded.

Considering this, the most likely condition to create smaller cells would be (b) addition of TRK ligand and a drug that inhibits the activity of the phosphatase that acts on SZE, since this would enhance the activity of the signaling pathway that leads to Pig1 production, which is known to regulate cell size.