Cell Signalling Flashcards
What causes the activation of the Synthesis of cAMP?
G-protein coupled receptors have a very characteristic structure, with what specific feature
- It has these 7 transmembrane domains (7 stretches of hydrophobic amino acids)
- Zig-zags through the membrane (4 extracellular - where ligands bind and 4 cytosolic regions)
There are two main types of G-proteins, what are they?
- Monomeric
- Trimeric
What affect does GTP have on these G-proteins
- Inactive when GDP bound
- Active when GTP bound
- GTP becomes hydrolysed when the protein needs to deactivate
What is the use of Guanine nucleotide exchange factors (GEFs)
Activate the G protein by stimulating it to release GDP
What is the use of GTPase activating proteins (GAPs)
Inactivate the G protein by stimulating hydroloysis of GTP to GDP
Keep in mind these proteins will be regulated by allosteric effectors ect
The Trimeric G protein is made up of how many subunits
3: α, β, γ
β, γ subunits are tightly complexed
Which face is the G-protein attached to?
The cytoplasmic face of the plasma membrane
Which parts of the G-protein is it activated and inactived
- Activation of G-protein, via receptor activation
- Inactivation of G protein by GTP hydroloysis by α-subunit
Binding of a ligand to the GPCR on trimeric G-protein does what?
- Binding of ligand to GPCR changes the conformation of the receptor
- Allowing GDP to be exchanged for GTP (acts as a Guanine nucleotide exchange factor)
- α and β subunits may dissociate
- Activated G-protein elicits a second messenger system
Cyclic AMP is produced from ATP and which other molecule
Adenylyl cyclase, releasing pyrophosphate
What causes the mechanism for the synthesis of cAMP to shutdown
Hydrolysis of GTP to GDP causes Gs protein to dissociate from adenylyl cyclase and bind to Gb instead
What causes the activation of the synthesis of cAMP?
- Binding of Hormone/Lingand produces a conformation chaning in receptor
- Receptor bind to Gs protein
- Binding to the receptor induces a conformational change in Gs
- GDP bound to Gs is replaced by GTP and subunit dissociates
- Gs binds to adenylyl cyclase, activating synthesis of cAMP
What affect does the synthesis of cAMP have
Activates cAMP-dependent protein kinase A (PKA)
PKA exists in inactive form but binding of cAMP causes dissociation of regulatory subunits
What is the job of PKA
PKA can phosphorylate target proteins
(e.g. metabolic enzymes in glycogen metabolism)
It has also influence transcription factors (CREB) and encorage transcription of genes
Receptor Tyrosine Kinases (RTKs) are different types of cell surface receptor is a
Enzyme coupled receptor
It puts phosphates on tyrosine
Receptor Tyrosine Kinases (RTKs) are involved in activating signalling pathways involved in…
- Cell cycle
- Cell metabolism
- Cell proliferation
- (known because mutations in receptors and/or singalling molecules linked to many cancers)
Receptor Tyrosine Kinases have 60 different genes which encode them with 16 structural subfamilies
Describe the basic features of the Tyrosine kinase receptor?
- Single transmembrane protein
- Extracellular ligand binding domain
- Intracellular tyrosine kinase domian
How does the receptor tyrosine kinase become activated
- Ligand binds to extracellular binding site
- Causes the receptor chain to dimerize
- Phosphorylate tyrosine residues on cytosolic domian
One tyrosines on the receptor tyrosine kinases have been activated, what can then happen
- Phosphorylated tyrosines can act as docking sites for a wide range of intracellular signalling proteins (which may become phosphorylated themselves turing on next protein in pathway)
- Specific intracelluar proteins will bind to specific phosphorylation sites on activated receptor
With the phosphorylated tyrosine proteins acting as docking stations for different proteins, what can this allow to happen
- Docking proteins may become phosphorylated (and activated) and in turn activate next protein in pathways
- OR docking protein may move closer to next protein in signalling pathway and cause it to be activated (resulting in signal being propagates through the cytoplasm into nucleus)
How can the receptor tyrosine kinase be turned off
- Dephosphorylation of tyrosine residues on the RTK
- Endocytosis of receptor
- Dual-specificity phosphatase will inactivate MAPKs
- GTPase activity can inactivate G-proteins
