CS - L2 Flashcards
What are the three general strategies used to transfer information across the plasma membrane
intracellular receptors
ion coupled channels
transmembrane receptors
What sort of molecules interact with intracellular receptors - give an example
small, hydrophobic molecules/ (g) - steroid hormone/NO
Describe the interactions of intracellular receptors
1 form complex-ligand receptor = active = complex translocates into the nucleus where it acts as/activates a txn factor = responsive genes
How fast is the response by communication via intracellular receptors?
relatively slow
What are ligand-gated ion channels or Ion-coupled
channels or Ion-channel-coupled receptors?
transmembrane pores, MULTIPLE proteins
What sort of molecules interact with ligand-gated ion channels, ion-coupled channels or ion-channel-coupled receptors - give an example
ions, Na+, Cl-, Ca2+.
What is the role of ligand-gated ion channel/ion-coupled channels/ ion channel-coupled receptors
converts chemical signal (neurotransmitter) into electric signals (ion flow0
How fast is the response by communication via intracellular receptors?
Very rapid & transient = change in membrane potential = exciting postsynaptic target cell
Why can’t most signal molecules cross plasma membrane?
large and/or hydrophilic
What is the cell surface receptor structure
???
What are the two common strategies used to transfer signals
conformational changes & clustering
What are the three main classes of transmembrane receptors?
G protein coupled receptors, enzyme-linked receptors, cytokine receptors
Describe the 7 transmembrane G-protein coupled receptors
Coupled with large protein G
What sort of activity do enzyme-linked receptors have?
Catalytic activity
Do cytokine receptors have any catalytic activity
No
What are cytokine receptors coupled with
intracellular enzymes
What is the largest family of cell surface receptors in eukaryotes?
G protein coupled receptors
How many isoforms do GCPR’s have
800
How many transmembrane alpha helices does GCPR have
7
How many loops bind the ligand?
3
What sort of change does ligand binding to receptor cause in GCPR?
Conformational change
What happens as a result of conformational change after the binding of ligand to GPCR
G protein is activated
What does the G protein act as?
On/off switch.
When is G protein active
If GTP is bound to G protein
How can GPCR amplify the signal
GPCR can interact with multiple G proteins
Heterotrimeric GTP-binding proteins are composed of how many subunits?
3
What are the three subunits?
alpha, beta and gamma
What is G protein bound to when inactive?
GDP
What happens to GDP after GPCR binds to its ligand
GDP replaced by GTP, making G protein active
What does G protein dissociate with when GDP is being replaced with GTP
Beta and gamma
What does protein alpha subunit do after GTP replaces GDP?
migrates to target protein, activating target protein
Give an example of GPCR-ligand interaction
epinephrine receptor - response to stress
What is the ligand in epinephrine receptor - response to stress
epinephrine (adrenaline)
What is epinephrine secreted by?
Adrenal glands
What sort of responses are a result of epinephrine response to stress?
increased heart rate, dilation of blood vessels, increase in blood glucose through glycogenolysis stimulation in liver cells, inhibition of insulin release by pancreas
What sort of ligands do RTK bind to
growth factors and hormones
How many membranes do RTK span
1
What does the cytoplasmic side of the RTK consist of
tyrosine kinase domain
what are the 2 forms of RTK
Monomeric inactive
Dimeric active
What does autophosphorylation do?
catalytic efficiency of the receptor and provides binding sites for the assembly of downstream signalling complexes
What can receptor tyrosine kinase trigger?
multiple signal transduction pathways
Give an example of common signalling pathways activated downstream of RTK RAF/MAP kinase
MAP kinase, AKT signalling and PLC-gamma mediated signalling
What are the RTK activatin steps
- dimerisation
bivalent ligand binds simultaneously - Tyr kinase activated
autophosphorylation of Tyr domains - RTK + protein = cellular response
What is EGF
epidermal growth factor
What is EGF involved in?
angiogenesis, apoptosis, cell proliferation, metastasis
What sort of receptor does EGF interact with
RTK
What are the common reasons behind
Activating mutation
Increase gene copy number
Overexpression
Truncation of receptor EC domain
What are cytokine receptors activated by
cytokines/GF
What do cytokine R do?
control synthesis and release inflammatory mediators
What are the three main components of cytokine receptors
receptor, JAK (janus kinase) and STAT (signal transducer & activators of txn)
What does the receptor do?
Binds to ligand & R forms a dimer
What happens to JAK after cytokine receptor after R forms a dimer
phosphorylates
- itself, R and STAT= activating STAT
What do STATs do
dissociate from receptor, dimarise - > moves to nucleus binds to promoter region = activation of txn
What is leptin
a hormone - statiety hormone
What is leptin made by
adipose tissue
What is the impact of leptin
reduces food intake, controls metabolism and body weight and is also involved in regulation of immune function
