Receptors and cell signaling Flashcards
effectors
alter the activity of different components downstream
and generate secondary messengers.
Endocrine signal
-signal (hormone) is transported via blood. Example epinephrine -long distance signaling - half life on min scale -freely diffusing signals
paracine signal
-signal (paracrine
factor) diffuses to neighboring
target cell of a different cell
type. Example testosterone
– Local signaling
– Short-lived signals
autocrine signal
secreting cells express surface receptors for the signal. Example interleukin-1 - Or release to cells of the same type -common in chemokines -growth factors in cancer cells
direct/juxtacrine signal
signal binds to signaling cell which then binds to receptor on the target cell. Example heparin- binding epidermal growth factor -immune cells
hydrophilic signaling
-cannot penetrate the plasma
membrane
-Interact with specific receptors at the cell surface.
• Examples: epinephrine, insulin, glucagon etc
-initiate second messenger
receptors in hydrophilic signaling
1) G protein - coupled receptors (GPCRs)
2) Receptor tyrosine kinases (RTKs)
lipophilic signaling
-Lipophilic signals pass through plasma membrane of target cell
-Examples: steroid hormones, thyroid hormone and retinoids.
- Signal (ligand) binds to specific receptor proteins inside the cell.
-Signaling molecule - receptor complex acts as a transcription
factor
-long half lives
cytoplasmic receptors
The hormone-receptor complex translocates to
nucleus where it binds to a specific DNA sequence called the hormone
response element (HRE) in the promoter region of specific genes.
nuclear receptors
already present in nucleus bound to DNA. The hormone
allows for interactions with additional proteins and activate the complex.
which substance acts through G protein coupled receptors
epinephrine
which substance acts through RTKS
insulin
what is the structural motif of GPCRS
– Extra Cellular Domain (ECD) - binds to signal – Trans Membrane (TM) Domain -composed of 7 α helices – Intracellular Domain (ICD) - interacts with G proteins
guanine nucleotide exchange factor (GEF)
makes G protein active by exchanging GDP for GTP
GTP-ase activating protein (GAP)
makes G protein inactive by hydrolyzing GTP to GDP
cGMP phosphodiesterase
hydrolyzes cGMP to 5’ GMP
what do inhibitors of cGMP PDE like viagra do?
- increase conc of cGMP
- leads to smooth muscle relaxation
- vasodilation
how do nitrates lower BP
- produce cGMP from activated guanylate cyclase
-leads to smooth muscle relaxation
vasodilation
what are examples of Gs GPCR signaling
- epinephrine
- histamine
what are ex of Gi GPCR signaling
- epinephrine/norepinephrine
- dopamine
what are ex of Gt GPCR signaling
- light and rhodopsin
what are examples of Gq GPCR signaling
-acetylcholine
what does Gs GPCR signaling activate
- activates AC
- which activates CaMP
- which activates PKA
- phosphorylates target
what does Gi GPCR signaling inhibit
- inhibits AC
- PKA not activated
- targets not phosphorylated
What does Gt GPCR signaling stimulate?
- cGMP PDE (phosphodiesterase)
- breaks cGMP
- turns signal off
What does G1 GPCR signaling activate?
- activates PLC
- breaks PIP2 into IP3 and DAG
- DAG activates PKC (phosphorylates)
- IP3 to ER to release Ca2+
cholera- how G proteins affected
- GS alpha subunit stays active
- continuously stimulates adenylate cyclase
- overproduction of cAMP
pertussis - how G proteins affected
- prevents dissociation of alpha subunit from complex (Gi alpha)
- less inhibition of AC
- overproduction of cAMP
G protein Receptor Kinases (GRKs)
-phosphorylate the GPCRs
-Arrestin binds to the to the 3rd intracellular loop
• Prevents Gα from interacting with the third loop
• Result is that Gα-GDP does not get converted to Gα-GTP; i.e.
inactivated G protein complex
what does RTK signaling lead to
alteration in gene transcription and protein activity
what does binding of ligand to ECD of RTK cause
dimerization
-phosphorylates tyrosine residues
what is RaS dependent signaling facilitated by?
-mitogen-activated protein kinase (MAPK) family
