Lecture 18: Signalling through enzyme linked receptors Flashcards
What receptors are involved with intrinsic enzymatic activity?
Receptor tyrosine kinases
Receptor serine/threonine kinases
What receptors are involved with linked enzymatic activity?
Cytokine receptors
What are kinases?
Enzymes that transfer a phosphate to a protein for phosphorylation
What are phosphatases?
Enzymes that remove phosphates from a protein
How do protein kinases work?
Catalyse the covalent modification of amino acids with OH groups using a phosphate from ATP
What is the role of phosphorylation and de-phosphorylation?
Molecular switches
How does signal transduction from protein phosphorylation usually occur?
In a cascade
How are RTK dimers stabilised?
Signal molecules
What is the process of RTK activation?
- Dimerisation brings intracellular kinase domains in contact
- Kinases are activated
- They phosphorylate each other on multiple tyrosines
How does signalling using RTKs occur?
- Phosphotyrosine residues make docking sites
- Association with and activation of downstream signalling proteins in receptor tails
- Generates signalling complex
How does termination of RTKs occur?
- Phosphate removal by protein tyrosine phosphatases
- Receptor endocytosis and degradation in lysosome
What is RAS?
Monomeric G protein that acts as a molecular switch downstream of RTK
How does RTK activate RAS?
Causes RAS to bind to GTP
This activates it
How does RTK activate RAS using GRB2/SOS?
- Phosphorylated RTK attracts GRB2 to PM
- GRB2 binds to SOS and activates it
- SOS converts RAS-GDP to active RAS-GTP
- This activates downstream pathways like MAPK
What happens when MAPK phosphorylation causes phosphorylation of enzymes?
Alters cell metabolism
Alters response to stimuli
