Receptors And Cell Signaling Flashcards
Endocrine Signaling
Signal (hormone) is transported via blood.
Ex. Epinephrine
- released by adrenal medulla acts on heart muscle
- long distance signaling
- short lasting: half-life on minute scale
- freely diffusing signals
Paracrine Signaling
Signal (paracrine factor) diffuses to neighboring target cell of a different cell type
Example: Testosterone
- Leydig cells synthesize and secrete testosterone induces spermatogenesis by acting on Sertoli and germ cells
- local signaling
- short lived signals
Autocrine signaling
Secreting cells express surface receptors for the signal
Example: Interleukin-1
- release to cells of same type as well
- common in chemokines: interleukin-1 produced by T-lymphocytes promote their own replication in immune response
- growth factors in cancer cells
Direct/Juxtacrine
Signal released and binds to receptor on target cell; signal acts like bridge between two cells (forming pair of cells that talk to each other)
Example: heparin-binding epidermal growth factor
- HB-EGF binds to EGF receptor
- immune cells
Gs
Stimulates adenylate cyclase (GPCR signaling)
-signals bind to GPCR and causes activation of G protein, exchange for GDP—> GTP, activation, alpha subunits separating from beta-gamma
-linked to adenylate cyclase (makes cAMP, a secondary messenger molecule), which actives PKA, which phosphorylates target proteins
Example:
- epinephrine binds b-adrenergic receptor
- histamine (allergic reactions)
Cell signaling Steps
- Cell synthesizes and secretes signaling molecules in response to a stimulus
- Signaling molecule (ligand) transported to target cell, where it binds to a specific protein (receptor)- localized on plasma membrane
- ligand-receptor complex activates or inhibits cellular pathways
- Effectors alter activity of diff. components downstream and generate secondary messengers that elicit a particular cellular response
- signal terminated by removal of signaling molecule and/or receptor attenuation/inactivation of signaling events
Hydrophilic
- water soluble
- cannot penetrate the plasma membrane
- interact with specific receptors at the cell surface
- Examples: epinephrine, insulin, glucagon, etc. (peptide hormones)
- signaling molecule-receptor complex imitates production of second messenger inside cell; generally small and derived from AA, polypeptides, or through lipid metabolism
- triggers downstream cellular response
- receptors involved: GPCRs and receptor tyrosine kinases (RTKs)
Lipophilic (hydrophobic)
- lipid soluble
- can pass through plasma membrane of target cell
- Examples: steroid hormones, thyroid hormones, and retinoids
- Signal (ligand) binds to specific receptor proteins inside cell
- signaling molecule- receptor complex acts as TF
- receptors located in cytosol or nucleus
- several families of DNA binding TFs: cytoplasmic receptors (interacts with HRE in promoter region) and nuclear receptors (already present in nucleus bound to DNA); long half lives and regulate txn of specific genes
G proteins and signaling
Resting condition- G protein is present in GDP-dominant form (inactive); bound to beta and gamma subunits; GAP accelerates hydrolysis of GTP–> GDP terminating signal
activated- GDP–> GTP (via action of GEF); GTP-bound it separates from beta and gamma subunits
GPCR signaling
- signaling molecule (ligand) binds to the ECD/ receptor and causes a conformational change in GPCR
- GPCR able to interact with and bind to G protein
- receptor then acts as a GEF (help activate G protein)
- ICD activates its G protein by triggering of GDP for GTP
- activated G protein (i.e. GTP-bound with only alpha) interacts with membrane-bound effector protein (activates or inhibits it), typically an enzyme that produces a secondary messenger
- Effector molecules catalyze reactions that produce secondary molecules
- signaling is terminated by various mechanisms: dissociation of signaling molecule, inactivation of G protein, reduction of concentration of secondary messenger
Gt
- stimulates cGMP phosphodiesterase
- signal= light (rhodopsin is a g protein) which will change conformation of GPCR
- stimulating cGMP phosphodiesterase (breaks cGMP- second messenger molecule)
- in absence of light, secondary messenger is already on techniquelly
- cGMP= channels are CLOSED
Example: -Light (Rhodopsin)
Gi
- inhibits adenylate cycle
- cAMP not being generated so pKa not activated; targets are not phosphorylated so different series of events
Example:
- Epinephrine/ norepeniphrine at alpha adrenergic receptor
- Dopamine at D2 receptor
Gq
- activates phospholipace C
- works through phospholipids C system
- enzyme activated in PLC- breaks PIP into IP3 and DAG
- DAG goes onto activate PKC which will phosphorylate multiple different products
- IP3- opens Ca gated channels releasing Calcium
- elevation of Calcium will activate Calcium calmodulin complex
Example:
-Acetylcholine at muscarinic acetylcholine M3 receptor
Cholera
cholera toxin prevents inactivation of Gs-alpha
A. consumption of contaminated water
B. covalent modification of alpha subunits ATP ribosylation of Arg, decreases GTPase activity
C. Gs-alpha remains active and continuously stimulates adenylate cyclase, resulting in overproduction of cAMP
D. overabundance of cAMP in intestinal cells open Cl-channels, leading to loss of electrolytes and water–> Diarrhea
Pertussis (whopping cough)
toxin prevents activation of Gi-alpha
A. ADP ribosylation of Cys on Gi-alpha prevents activation and dissociation of alpha subunit from the G protein complex
B. less inhibition of AC and overproduction of cAMP
C. loss of fluids and excessive mucous in airway epithelial cells
