Cell signalling

What is it?

A transmembrane dimer protein that binds ligands extracellulary. it has 2 binding regions which can bind to 2 ligand and thus trap them as the proteins intracellular domains come together.

How does it work?

1. Intracellular kinase domains are inactive in monomer form

2. Lignad binds causing dimerisation of the receptor, bringing the 2 kinase domains together which activates them.

3. The domains phosphorylate each other causing conformational change to one another allowing them to become the binding site for intracellular signalling proteins to carry the signal down.

How do the kinase domains phosphorylate each other?

Using GTP, the domains are bound to GDP in their monomeric form and once the ligands bind it causes GDP to be exchanged for GTP by a GEF.

What is it/ what are its components?

A receptor that spans the membrane 7 times. It has an extracellular domain that binds to ligands and an intracellular domain which is connected to a G-protein. the G-prtoein is a trimeric peripheral membrane that consists of 3 sub-units; alpha subunit (which binds to GDP/GTP), beta and gamma subunits.

How is the signal passed? 

1. The GPCR is sat on the membrane and Gproteins are placed near it. 

2. A ligand binds to the receptor causing conformational change, this activates the GPCR.

3. The activated GPCR can now recruit/bring closer the G-protein sat on the membrane.

4. When this happens, the G-protein gets activated as the GDP molecule bound to the alpha sub-unit is exchanged with a GTP molecule. 

5. The activated G-protein dissociates from the GPCR and can now further activate downstream molecules to pass the signal.

What makes this pathway speacial? 

Uses both switch mechanism, phosphorylation and monomeric G-Proteins.

How does it work?

1. RTK is sat on membrane and a ligand binds

2. Causes dimerisation and the kinase domains begin to phosphorylate each other producing a binding site.

3. This allows adaptor proteins to bind which in turn activates it so it able to activate the next molecule.

4. The next molecule is a Ras-activating protein

5. This protien activates a small Ras-protein that is sat on the inner leaflet by exchanging the GDP to GTP. 

6.This activated Ras-protein can further activate downstream molecules.