Receptor Signaling Pathways Quiz

Receptor Signaling Pathways

• Four Main Receptor Classes:
  • Ligand-gated ion channels
  • G-protein coupled receptors (GPCRs)
  • Enzyme-linked receptors
  • Nuclear receptors

G-Protein Coupled Receptors (GPCRs)

• Activation: GPCR activation leads to GDP being exchanged for GTP on the G protein's alpha subunit.

• Dissociation: The activated Ga-GTP subunit separates from the By complex.

• Adenylate Cyclase Activation: Ga-GTP activates adenylyl cyclase (AC).

• cAMP Production: AC converts ATP to cyclic AMP (cAMP), a second messenger.

• Protein Kinase A (PKA) Activation: cAMP binds to PKA's regulatory subunits, releasing the catalytic subunits and activating PKA.

• Phosphorylation: Activated PKA phosphorylates target proteins, initiating cellular responses.

• Gs and Gi Subunits:

  • Gs (stimulatory) activates AC.
  • Gi (inhibitory) inhibits AC.

• Bacterial Toxins:

  • Cholera toxin modifies Ga (activates) leading to excessive cAMP and diarrhea.
  • Pertussis toxin modifies Gai (inactivates), blocking inhibition and increasing cAMP levels.

Gq/11 Subunits

• Phospholipase C (PLC) Activation: G protein-coupled receptors containing q/11 subunits activate PLC.
• PIP2 Cleavage: PLC cleaves phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG).
• Calcium Release: IP3 releases calcium from the endoplasmic reticulum into the cytoplasm.
• Protein Kinase C (PKC) Activation: DAG activates PKC in the membrane.
• Calcium Signaling: Calcium, bound to calmodulin (CaM), activates CaMKs.
• Cellular Responses: These include smooth muscle contraction, muscle contraction, gene expression.

Enzyme-Linked Receptors

• Receptor Tyrosine Kinases (RTKs):
  • Dimerization: Ligand binding causes receptor dimerization.
  • Autophosphorylation: The receptors phosphorylate each other.
  • Phosphotyrosine motifs: These attract intracellular signaling. molecules, initiating downstream responses like insulin-mediated glucose uptake.
• Receptor Guanylyl Cyclases: Convert GTP to cGMP (second messenger). ANP (atrial natriuretic peptide) binding leads to vasodilation.
• Receptor Serine/Threonine Kinases: These receptors use phosphorylation cascades to regulate cellular functions. (e.g. TGFβ in cell proliferation).
• Tyrosine Kinase-associated receptors: These receptors activate associated tyrosine kinases (e.g., JAK2) triggering similar signaling cascades.

Receptor Tyrosine Phosphatases

• Dephosphorylation: These receptors remove phosphate groups from target proteins, reversing signaling pathways.

GPCRs vs RTKs

• Structure: GPCRs have seven transmembrane helices, whereas RTKs have one transmembrane helix.
• Enzymatic Activity: GPCRs lack intrinsic enzymatic activity; RTKs have catalytic activity.
• Dimerization: GPCRs generally do not require receptor dimerization; RTKs often do.
• Signaling Mechanism: GPCRs utilize secondary messengers; RTKs activate phosphorylation cascades.
• Duration of Signaling: GPCRs typically initiate seconds-long responses while RTKs can trigger hours-long effects.

Test your knowledge on receptor signaling pathways, focusing on G-protein coupled receptors (GPCRs). This quiz covers key concepts such as GPCR activation, cAMP production, and the role of various G-proteins. Dive into the details of how these receptors contribute to cellular responses.