Receptors and Cell Signaling Flashcards
Endocrine signaling
Hormone is transported via blood (ex: epinephrine). Used for long distance signaling. Long lasting half-life on minute scale.
Paracrine signaling
Signal (paracrine factor) diffuses to neighboring target cell of a different cell type (ex: testosterone). Used for local signaling. Short-lived signals.
Autocrine signaling
Secreting cells express surface receptors for its signal ex: interleukin-1). Can be growth factors in cancer cells.
Juxtacrine/Direct signaling
Signal binds directly to receptor on the target cell (ex: heparin-binding epidermal GF). Common in immune cells.
Hydrophilic signaling
Cannot penetrate the PM, therefore interact with receptors on cell’s surface. They employ a second messenger system.
Lipophilic signaling
Can penetrate the PM and binds to a receptor inside the cell. The molecule-receptor complex acts as a transcription factor.
Cytoplasmic receptors
Receptors in lipophilic signaling. Creates a hormone-receptor complex that translocates to the nucleus where it binds to a specific DNA sequence called the hormone response element (HRE) in the promoter region.
Nuclear receptors
Receptors in cytoplasmic signaling. They are already present in the nucleus bound to the DNA. The hormone allows for interactions with additional proteins and actviate the complex.
Types of receptors (3)
- enzyme-coupled receptor
- G protein-coupled receptor (GPCR)
- ligand-gated ion channel
Hydrophilic meds
Short half life and given at time of need (ex: epi).
Hydrophobic meds
Long half lives and need to be taken daily (ex: oral contraceptives).
Structural motif of GPCRs (ECD, TM, ICD)
- extra cellular domain (ECD) - binds to signal
- trans membrane domain (TM) - composed of 7 a-helices
- intracelular domain (ICD) - interacts with G protein
GPCR signaling overview (4)
- Ligand bonds to ECD and causes a conformational change in the GCPR.
- ICD activates its G protein by exchanging GDP for GTP.
- Activated G protein interacts w/ membrane-bound effector (usually an enzyme that produces a second messenger) and produces a response.
- Signal terminated.
Guanine nucleotide exchange factor (GEF)
Assists in exchange of GDP for GTP.
GTPase
Hydrolyzes GTP back into GDP, inactivating it.
GTPase-activating protein (GAP)
Accelerates intrinsic GTPase actvity.
Steps of G protein signal relay
Draw.
Inhibitors of cGMP and cAMP PDE
Increased conc. of cellular cGMP, causing smooth muscle contraction and vasodilation.
Caffeine inhibits cAMP PDE, causing increased HR.
NO and smooth muscle relaxation
NO produced in epithelium and is responsible to relax muscles via activation of guanylate cyclase, leading to the production of cGMP.
Cholera toxin
Toxin decreased GTPase activity, causing an overproduction of cAMP. Increased cAMP in intestinal cells open Cl- channels, causing dehydration.
Mechanism of water secretion (4)
- Toxin activates AC to produce cAMP.
- cAMP activates the CFTR.
- Cl- secreted as a result, Na+ follows.
- NaCl builds up and creates osmotic gradient which water follows.
RTKs structure (3)
- ECD - contains molecule binding site.
- Single helix - spans the membrane.
- ICD - possesses the tyrosine kinase activity.
Gs
Stimulates AC.
Gi
Inhibits AC.
Gt
Stimulates cAMP PDE.
Gq
Activates PLC.
Gq mechanism (post GTP phosphorylation)
GTP activates PLC, which cleaves PIP2 into IP3. IP3 causes release of Ca2+, which causes PKC to go to membrane and is activated by DAG.
Proteins/signal molecules involved in Gs pathway
AC, cAMP, PDE, PKA.
Proteins/signal molecules involved in Gt pathway
cGMP, 5’-GMP, cGMP PDE.
Proteins/signal molecules involved in Gq pathway
PLC, PIP2, IP3, Ca2+, DAG, PKC.
