Questions: Receptor Signaling Pathways (RTKs, GPCRs, and Second Messengers)

Question 1

When a growth factor binds to a receptor tyrosine kinase (RTK), what is the immediate molecular consequence?

• A. The receptor directly phosphorylates a transcription factor in the nucleus
• B. Two RTK monomers dimerize and phosphorylate each other on cytoplasmic tyrosine residues
• C. The receptor releases a second messenger (cAMP) into the cytoplasm
• D. A G protein exchanges GDP for GTP and dissociates from the receptor

Answer: (B)

Ligand binding drives dimerization of two RTK monomers, and the paired kinase domains then cross-phosphorylate each other (autophosphorylation) on cytoplasmic tyrosine residues. These phosphotyrosines become docking sites for adapter proteins like Grb2. The G protein exchange mechanism (option D) belongs to GPCR signaling, not RTKs.

Question 2

cAMP (cyclic AMP) is classified as a first messenger because it is the initial signal that activates an intracellular signaling pathway.

• T. True
• F. False

Answer: False

cAMP is a second messenger. First messengers are extracellular signals — hormones, growth factors, or neurotransmitters — that cannot cross the plasma membrane. Second messengers like cAMP, IP3, DAG, and Ca²⁺ are intracellular molecules generated in response to receptor activation. They relay and amplify the signal inside the cell.

Question 3

How does signal amplification occur in a GPCR-cAMP signaling cascade?

Model answer: A single ligand-bound GPCR can activate many G protein molecules; each activated Gαs subunit activates one adenylyl cyclase; each adenylyl cyclase produces many cAMP molecules; each cAMP activates protein kinase A (PKA); each PKA phosphorylates many substrate proteins. Each step multiplies the signal, so one receptor-ligand binding event can alter thousands of downstream proteins.

This cascading amplification is a defining feature of signaling pathways. It explains why hormones present at nanomolar concentrations can produce strong cellular responses — the signal is amplified at every enzymatic step. It also means the pathway must be tightly regulated (phosphodiesterases degrade cAMP; GTPase activity of Gα turns off G proteins) to prevent runaway signaling.