Lecture 13 - Intracellular Signalling Flashcards
List the steps of a signalling pathway:
Signal e.g. primary messenger/ligand
Receptor e.g. receptor proteins - changes its conformation
Transduction e.g. transducer proteins - convert signal from one form to another
Effect e.g. secondary messengers like cAMP
Response e.g. response protein
What is cross talk?
When different components trigger different pathways
One or more components of one signalling pathway can be used in another
They achieve specificity by affinity and trigger levels
What is endocrine signalling?
The signal is travelling in the blood to a distant cell, must be small
e.g. Insulin
What is paracrine signalling?
A secretory cell releases a signal, it then travels by diffusion and binds to receptors in target cells
What is autocrine signalling?
A signal is released from a cell and binds to receptors on the same cell
What are the two types of receptors?
Cell surface and intracellular
What molecules bind cell surface receptors?
Hydrophilic signalling molecules as they cannot cross the membrane
What molecules bind to intracellular receptors?
Hydrophobic signalling molecules (if they are small) as they can cross the cell membrane
What are the different types of cell surface receptor?
Ion-channel linked, Kinase-linked, G-protein coupled
What is the structure of G-protein coupled receptors?
7 membrane spanning domains
G-protein binding domain is the C terminus
Signal interacts with N-terminus and exoloops
There are 3 exoloops, 1 and 2 are joined by disulphide bonds
There are 3 cytoloops inside the cell, sometimes get a 4th through post translational modification
What is another name for G-protein receptors?
Metabotropic
What is another name for ion-channel linked receptors?
Inotropic
How is a signal generated with GPCR?
Signal molecule binds to the receptor, which causes a conformational change in the GPCR
This causes the GPCR to interact with the G-protein
The G-protein is made of an alpha, beta and gamma subunit
The beta and gamma subunits are linked
Before activation the alpha subunit is bound to GDP, so it is inactive
Once activated by the signal the GDP is phosphorylated to GTP
The alpha and beta-gamma subunits then separate, they stay attached to the membrane which increases the chances of them interacting with their target
To reset the system alpha subunit looses GTP and rebind GDP
What are IP and Diacylglycerol, where are they and what do they do?
Secondary messengers, remain in the membrane, and activate Protein Kinase C and affect calcium stores
What is cAMP, where does it go and what does it do?
Secondary messenger, released into the cytoplasm, activates Protein Kinase A