Lecture 24 - Cell Communication 1 - Signal Transduction Flashcards
What is signal transduction and why does it occur?
L24 S2+4
- cell to cell communication
- coordination in development and metabolism
What are the two major types of responses that occur as a result of signal transduction?
(L23 S6)
Fast response:
-change in activity or function of proteins
Slow response:
-change in amounts of protein by changing gene expression
What are the types of signaling and what differentiates them? (5)
(L23 S 10-14)
Endocrine:
- signal released into blood stream to reach distant target
- long lived signal
Paracrine:
- signal release into intracellular space and acts on nearby cells
- short lived signal
Synaptic
- neurotransmitter released from axon terminal and affects target cell
- short lived signal
Autocrine:
- signal released into extracellular space and binds its own receptor
- eg. cancer growth factors
Direct:
- binding of signal attached to one cell to receptor attached to another cell
- eg. immune cells
What different responses can cells have to signals? (4)
L23 S 16
- survive
- grow/divide
- differentiate
- die (apoptosis)
What components are involved in a signal cascade?
L23 S17
Signals (ligand)
Receptors:
-bind specific signal molecules
Effectors:
-change activity due to binding of signal to receptor
What types of molecules can be signal molecules?
L23 S18
- proteins
- small peptides
- amino acid derivatives
- hydrophobic molecules (steroid hormones)
What are the different classifications of receptors involved in cell signaling?
(L23 S22)
Cell surface:
- extracellular domain: binds signal molecule
- transmembrane domain: anchors receptor
- cytoplasmic domain: initiates signal
- major class is G-protein coupled receptors
Intracellular receptors:
- in the cytosol
- binds steroid hormones
- typically alter gene expression and have DNA binding domain
What are the components of a G-protein coupled receptor pathway?
(L23 S28)
G-protein coupled receptor (GPCR):
- bind signal molecule
- 7 transmembrane α helices
- activates G-protein
G-protein:
- 3 subunits (α, β, and γ)
- associated with inner membrane
- binds GTP/GDP
Effector:
- eg. adenyl cyclase
- generates second messengers (eg. cAMP)
What are the steps involved in a G-protein coupled receptor pathway?
(L23 S33-37)
- Ligand binds GPCR
- GPCR undergoes conformational change
- GPCR binds G-protein
- GPCR acts as GEF for G-protein
- α subunit of G-protein releases GDP and binds GTP; activated
- G-protein binds effector protein and activates it
- Effector (adenyl cyclase) catalyzes second messenger formation (cAMP)
GTP eventually is hydrolyzed and deactivates G-protein
What affect does cholera have on the body?
L23 S45
- cholera toxin binds G-protein and makes it always active
- results in pumping of Cl- and water into intestine resulting in severe diarrhea
What effect does cAMP have downstream?
L23 S48
- cAMP activates cAMP-dependent protein kinases (PKA)
- PKA consists of two regulatory subunits and two catalytic subunits
- binding of cAMP to regulatory subunits causes release of active catalytic subunits
- catalytic subunits act as kinases
What affect can phosphorylation (kinase activity) have on a protein? (4)
(L23 S49)
- addition of two phosphates can alter protein conformation
- form structure which other proteins can recognize
- can activate or inactivate enzymes
- alteration of localization of proteins
Epinephrine induces activation of __________.
L23 S50
PKA
What are the different ways desensitization can occur? (5)
L23 S56-58
- Receptor sequestration; formation of endosome containing receptors
- Destruction of receptors; fusion of endosomes with lysosomes
- Hormone levels drop; results in decreased PKA activity
- Remove signal molecule
- GRKs (G-protein receptor kinases); inactivation of GPCR
Describe the process by which GRKs desensitize a signal.
L23 S58
- GRKs phosphorylate GPCR
- phosphorylated GPCR allows for the binding of arrestin
- arrestin blocks binding of α-subunit of G-protein from binding GPCR
- without GEF activity G-protein remains inactive
