Receptor And Signaling Supplement (3) Flashcards
What is endocrine signaling
Signal (hormone) transported via blood
Long distance and short acting
Freely diffusing signals
Paracrine signaling
Signal (paracrine factor) diffuses to neighboring target cell of a different cell type
Local short lived signaling
Autocrine signaling
Secreting cells express surface receptors for the signal
Ex. Is growth factor in cancer cells
Direct/juxtacrine signaling
Signal binds to signaling cell which then binds to receptor on the target cell
How long is short-term signaling
Seconds to minutes
How long is long-term signaling
Hours to days
Can hydrophilic signals penetrate the plasma membrane?
No
Examples of hydrophilic signaling
Epinephrine, insulin, glucagon
How do hydrophilic signals work
Signal binds with specific cell membrane receptor
Initiates production of secondary messenger within cell (generally small and derived from AA)
What two receptors are involved in hydrophilic signaling
G proteins
RTKs
How does lipophilic signaling work
Lipophilic signals pass through plasma membrane and bind to specific receptor proteins within cell
Molecule-receptor complex acts as a transcription factor
Typically have long half-lives
Cytoplasmic recpetors
Is a DNA binding transcription factor
Exists in an inactive state with HSP 90
Upon binding to ligand, HSP dissociates
How many subunits are in a trimeric G protein
3
Aby
To become active, what does GPCR have to do
It must exchange its GDP for GTP
This occurs via the action of guanine exchange factor (GEF)
How does GPCR return to inactive state?
G protein hydrolyzes GTP back to GDP using GTPase-activating protein (GAP)
How do toxins fuck up the CFTR
Toxins activate adenyly cylcase which makes cAMP from ATP
Excess ATP opens CFTR and then they whole water thing begins
Beta-adrenergic receptor
Is a Gs GPCR (stimulates adenylate cyclase)
Causes:
Relaxation of bronchial and intestinal smooth muscle
Contraction of heart muscle
Glycolysis in muscle
Histamine H2 recpetor
Is a Gs GPCR
Causes allergic reaction and release of histamines
Alpha-adrenergic receptor
Is a Gi GPCR
Causes constriction of smooth muscle
Dopamine D2 Receptor
Is a Gi GPCR
Causes increased HR
Muscarinic acetylcholine M2 receptor
Is a Gq GPCR receptor
Causes brochoconstriction and stimulation of salivary glands
What are the different ways to desensitize a mechanisim
- Drop hormone levels - decreased adenylyl cyclase activity leads to decrease cAMP and decreased PKA activity
- Remove the signaling hormone - phosphodiesterase will remove cAMP
- Receptor sequestration with an endosome
- Receptor destruction with an endosome and a lysosome
Three parts of RTK
ECD - contains signaling molecule binding site
Single Helix that spans the membrane
ICD - possesses tyrosine kinase activity
Steps in RTK signaling
- Binding of ligand to ECD causes dimerization which phosphorylates the tryosine residue
- Phospho-tyrosines are recognized by adapter and two docking proteins (SH2) and docking protein targets in cytoplasm through RAS-dependent (MAPK)
- Triggers phosphorylation of protein targets in the nucleus, plasma membrane, and cytoplasm. This leads to alteration in gene transcription and protein activity
- Signal terminated by degradation of ligand
RAS independent pathways uses what type of molecule in signaling?
Another type of kinase
