Learning Objective

Understand the structure, function, and signaling mechanisms of transmembrane enzyme receptors, including receptor tyrosine kinases and guanylyl cyclase–associated receptors.

Receptor Tyrosine Kinases (RTKs)

Function: Mediate signaling for insulin and growth factors (e.g., EGF, PDGF).

Structure:

• Extracellular domain: Binds ligand (insulin or growth factors)
• Transmembrane domain: Anchors the receptor in the membrane
• Cytoplasmic domain: Functions as a tyrosine kinase

Mechanism:

1. Ligand binds to the extracellular domain.
2. The receptor undergoes dimerization or conformational change.
3. The tyrosine kinase domain is activated.
4. Tyrosine residues on the receptor and/or downstream substrate proteins get phosphorylated.

Outcome: Triggers tissue-specific signaling pathways → growth, differentiation, metabolism.

Guanylyl Cyclase–Associated Receptors

Function: Mediate effects of atrial natriuretic peptide (ANP).

Mechanism:

1. ANP binds to the receptor.
2. Activates guanylyl cyclase activity in the cytoplasmic domain.
3. Increases cyclic GMP (cGMP) levels.
4. cGMP triggers downstream signaling → vasodilation, natriuresis, and reduced blood pressure.

Activity