5 - RECEPTOR GUANYLYL CYCLASES AND ABNORMAL CELL GROWTH

Receptor guanylyl cyclases structure

Single-pass transmembrane proteins with an extracellular ligand-binding domain and an intracellular guanylyl cyclase domain.

Receptor guanylyl cyclases enzymatic activity

the intracellular domain converts GTP to cGMP, acting as a guanylyl cyclase

Receptor guanylyl cyclases secondary messenger produced

cGMP

Receptor guanylyl cyclases downstream targets

Protein kinase G (PKG)

Receptor guanylyl cyclases Kinase activated by cGMP

PKG, also known as cGMP-dependent protein kinase

Receptor guanylyl cyclases Systemic effects of activation (4)

1. Kidney - Natriuresis

2. Intestine - Chloride secretion, and smooth muscle relaxation

3. Heart - Vasodilation and lower blood pressure

4. Brain - Neural regulation

How can changes in signal molecules lead to cancer?

Mutations may lead to constitutive activity or loss of regulation.

How can receptor mutations lead to abnormal growth?

They can result in ligand-independent activation of signaling pathways.

How can G protein mutations lead to cancer?

Mutated Ras may lack GTPase activity, leading to persistent signaling.

How can kinase abnormalities contribute to oncogenesis?

Overactive kinases can cause excessive proliferation.

What are oncogenes?

Mutated genes, often from viruses, that encode dysfunctional signaling proteins.

What is the role of defective Ras in cancer?

Loss of GTPase activity in Ras leads to continuous stimulation of the MAPK cascade.