Cell Signaling (I & II) Flashcards
What are the two general types of signal receptors?
Cell-surface receptors and intracellular receptors
Describe the structural differences between extracellular and intracellular signaling molecules
Extracellular signaling molecules are large, hydrophilic signals that cannot enter the cell.
Intracellular signaling molecules are small hydrophobic molecules that can pass through the lipid membrane and often into the nucleus
What are the different ways that cells can transmit signals?
Contact-dependent: cells must physically touch
Paracrine: cells release signal that acts locally
Autocrine: cell releases signal that act on itself
Synaptic: neurotransmitter released into synapse
Endocrine: hormone released into bloodstream, travels to target tissue
What determines the specificity of endocrine signaling?
The receptors expressed on target cell surfaces dictate which hormones are “pulled out” of the blood stream
How do survival signals differ from those leading to growth/division, differentiation, and apoptosis?
Different combinations of signals lead to all of these events
Signals in addition to the basic survival signal are required for growth/division, and different signals lead to differentiation
The absence of survival signals leads to apoptosis
How can one hormone induce numerous different responses in the body?
Hormones can have different types of receptors in different tissues
-Example: acetylcholine causes skeletal muscle contraction by acting on ion channels, decreases heart rate by acting on muscarinic M2 receptors in the heart, and lead to salivary gland secretion by binding to muscarinic M3 receptors
Describe the primary response following steroid hormones binding to their receptors
Primary response genes are activated by receptor-steroid-hormone complexes
Primary response proteins can feed back to downregulate primary response OR they can trigger secondary response by activating additional genes
Describe the structure of nuclear receptor superfamily proteins
All have a DNA binding domain, C-terminal that binds hormone, and an N terminal that interacts with regulator proteins
- Inhibitory proteins can block the ligand binding domain
- When hormone is bound, protein is activated, can interact with coactivator proteins and cause transcription of target genes
What are the major classes of cell-surface receptors?
Ion channel coupled receptors
Enzyme coupled receptors
G-protein coupled receptors
Describe the activation of enzyme coupled receptors
1) Signal dimer brings 2 inactive receptor monomers together and activates them
2) Enzyme is activated, phosphorylate each other and then other proteins
True or false: The enzyme activity of G-protein coupled receptors is regulated by phosphorylation
False
G-protein coupled receptors have no enzyme activity on their own
Describe the structure of a GPCR
7-transmembrane receptors with a N-terminal receptor region in the extracellular space, and a C-terminal cytosolic tail
3 intracellular loops are sites for phosphoylation
Where on the GPCR do hormones bind?
They bind to the N-terminal tail and extracellular loops
Small ligands bind deep within the plane of the membrane
Describe the structure of the G-protein
Made up of 3 subunits: α, β and γ
α is bound to GDP in inactive form, GTP when active
α and γ have transmembrane lipid tails
β and γ are tightly bound, act as a single functional unit
How are G-proteins activated?
When an extracellular signal binds to a GPCR, there is a conformational change that binds the G-protein and triggers the α subunit to break from GDP and pick up GTP. With GTP bound, the α subunit can dissociate from the βγ complex and each can transmit separate signals
When are G-protein target proteins active?
For as long as the α subunit is associated with it
The α subunit only associates with target proteins with GTP bound
How is the α subunit deactivated?
The α subunit has GTPase activity that is activated by target proteins causing the α subunit to turn itself off by hydrolyzing GTP
What are the 3 major G-protein types discussed in class and what are their functions?
Gs: activates adenylyl cyclase
Gi: inhibits adenylyl cyclase
Gq: activates phospholipase C-β
