Signal Transduction Flashcards
Q1: Define signal transduction and explain its importance in cellular function.
A: Signal transduction is the process by which cells respond to external signals through a cascade of molecular events, converting extracellular cues into intracellular responses. It regulates crucial functions like metabolism, gene expression, proliferation, and cell survival, and is integral to maintaining homeostasis and responding to environmental changes.
Q2: Describe the structure and activation mechanism of GPCRs.
A:
GPCRs are 7-transmembrane domain receptors that interact with heterotrimeric G-proteins.
When a ligand binds the receptor, it acts as a guanine nucleotide exchange factor (GEF), replacing GDP with GTP on the Gα subunit.
The GTP-bound Gα dissociates from the βγ subunits and activates downstream effectors like enzymes or ion channels.
Q3: How are Gα subunits classified and what are their signaling roles?
A:
Gαs: Stimulates adenylyl cyclase → increases cAMP → activates PKA.
Gαi: Inhibits adenylyl cyclase → decreases cAMP.
Gαq: Activates phospholipase C (PLC) → produces IP3 and DAG → IP3 mobilizes Ca²⁺, DAG activates PKC.
Q4: Outline the role of cAMP as a second messenger.
A:
Synthesized from ATP by adenylyl cyclase.
Activates protein kinase A (PKA), which phosphorylates various target proteins.
Influences transcription via phosphorylation of CREB (cAMP Response Element Binding protein).
Regulated by phosphodiesterases (PDEs), which degrade cAMP.
Q5: Explain the spatial and temporal regulation of the cAMP-PKA pathway.
A:
A-kinase anchoring proteins (AKAPs) localize PKA and PDEs to specific subcellular regions.
This compartmentalization ensures precise regulation of PKA activity and cAMP degradation, optimizing cellular response.
Q6: What is the significance of IP3 and DAG in Gαq signaling?
A:
IP3 binds to receptors on the ER to release Ca²⁺ into the cytosol.
DAG remains membrane-bound and, along with Ca²⁺, activates protein kinase C (PKC).
PKC then phosphorylates various target proteins, modulating cell activity.
Q7: Describe the structure and function of receptor tyrosine kinases (RTKs).
A:
RTKs are single-pass transmembrane receptors with intrinsic kinase activity in their cytosolic domains.
Ligand binding induces dimerization and autophosphorylation of tyrosine residues.
This recruits signaling proteins, initiating pathways that control proliferation, differentiation, and survival.
Q8: How is GPCR signaling terminated?
A:
Gα subunit hydrolyzes GTP to GDP, reassociating with the βγ dimer.
GPCRs may be phosphorylated by GPCR kinases (GRKs), leading to β-arrestin binding and receptor desensitization or internalization.
Q9: Provide an example of how GPCR dysfunction can cause disease.
A:
Usher syndrome: Involves mutations in GPCRs, resulting in combined deafness and blindness due to disrupted sensory signal transduction.
