Intracellular Signalling Pathways Flashcards
What is signal transduction?
Molecule binding to a receptor on a cell membrane that leads to a series of chemical reactions to elicit a larger cellular response
What is a receptor?
A protein (usually cell membrane) that binds a ligand to either directly or via signal transduction lead to a cellular response.
What are 4 examples of cellular responses that could happen in response to a ligand binding to a receptor?
Contraction, proliferation, secretion, differentiation
What are the three superfamilies of cell surface receptor (think KING but not the N as that’s nuclear not cell surface)
Kinase receptors
Ion channels (ligand)
GPCRs
What is a ligand? What is special about a ligand? Are they agonistic or antagonistic or both?
Ligands bind to receptors to elicit a cellular response. They are specific to that receptor hence they can elicit a very specific cellular response. They can be both.
How many alpha beta and gamma GProtein subunit types are there? How many combos of alpha-beta-gamma hetereotrimers could this make?
20 alpha
5 beta
12 gamma types
Could make more than 1000 combos of alpha-beta-gamma
Describe how GPCRs display diversity, specificity and amplification
Diverse range of ligands, receptors, G proteins and effectors - therefore diversity of cellular responses
Specific ligands, receptors, G proteins, effectors and pathways
Amplification of signal - small extracellular signal leading to a large intracellular response
How many GPCRs do we have? How much of the genome do they make up?
> 800
>2%
GPCRs respond to a large range of stimuli - name a few
Light Taste Odour Ions Neurotransmitters Peptide and Non peptide hormones Large glycoproteins (TSH)
Name 4 things about the structure of GPCR proteins.
Single polypeptide chain
7 transmembrane domains
N terminus extracellular
C terminus intracellular
How are the transmembrane domains linked?
With helices
Which two general places can ligands bind? Which size of ligand would usually bind at each of these? Is there an exception to this?
2-3 transmembrane domain (usually small ligands) N terminus (usually larger ligands although Glutamate binds here and its small)
What are the stages from a ligand binding to termination of GPCR mediated signal transduction?
Ligand binds to GPCR, conformational change in GPCR causes a change in the attached GProtein. Causes GDP on alpha subunit to dissociate and GTP binds in its place (also uses hydrolysis of GTP to do this). GTP binding to Alpha subunit causes beta-gamma subunit to dissociate. Each Alpha-GTP and beta-gamma units can then interact with their effectors - (normally either second messenger enzymes or ion channels). Termination via GTPase activity of Alpha subunit - hydrolysed it’s GTP to GDP+Pi. Alpha-GDP then re-associates with beta-gamma to form original Alphabetagamma heterotrimer.
Explain QISSQIQ
Q - alpha 1 adrenoceptor - alpha-Q subunit - activates PLC
I - alpha 2 adrenoceptor - alpha-I subunit - inhibits AC
S - beta 1 adrenoceptor - alpha-s subunit -activates AC
S - beta 2 adrenoceptor - alpha-s subunit -activates AC
Q - M1 - Alpha-Q - activates PLC
I - M2 - Alpha-i - inhibits AC
Q - M3 - Alpha-Q - activates PLC
Effectors can be enzymes or ion Channels - name 4 enzyme effectors and 2 ion channel effectors
AC, PLC, PI3K, cGMPphosphodiesterase
VOCCS, GIRKS (inwardly rectifying K+ channels)
