Enzyme Coupled Receptors Flashcards
What is the mechanism of activation of receptor tyrosine kinases (RTKs)?
Dimerisation brings intracellular kinase domains in contact, activating kinases
Dimerisation occurs when signal molecules stabilize RTK dimers.
How do phospho-tyrosine residues function in RTK signaling?
They create specific binding sites to allow association with and activation of downstream signaling proteins
This process generates a signaling complex.
What are the two main ways RTKs can be inactivated?
- Phosphate removal by protein tyrosine phosphatases
- Receptor endocytosis and degradation in the lysosome
What role does RAS play in RTK signaling?
RAS is a monomeric G-protein that acts as a molecular switch downstream of RTK at the plasma membrane
RAS activation is mediated by RTKs.
What are the key amino acids involved in phosphorylation by kinases?
- Serine
- Threonine
- Tyrosine
True or False: Phosphorylation and de-phosphorylation are irreversible processes.
False
They are reversible reactions that contribute to the dynamic nature of signal transduction.
What is the MAPK kinase cascade?
A signaling cascade organized by protein kinases controlled by phosphorylation
It is a key pathway influenced by RTKs.
What is the function of GRB2 in RTK-mediated RAS activation?
GRB2 binds to phospho-tyrosine residues and recruits SOS, a guanine nucleotide exchange factor (GEF)
This process activates RAS at the plasma membrane (does not involve direct binding or phosphorylation of RAS)
Fill in the blank: Protein phosphorylation acts as a _______.
[molecular switch]
What are the stages of signal transduction through cell surface receptors?
- Reception
- Transduction
- Response
What is the role of the PI3K pathway in RTK signaling?
It regulates cell survival, proliferation, migration, and differentiation
PI3K is a phosphatidylinositol 3-kinase.
What does the activation of RTKs lead to in terms of gene expression?
Altered expression of many genes involved in cell survival, proliferation, migration, and differentiation
How do different cell types respond to the same receptor activation?
They transduce signals differentially, leading to varied cellular responses
This differential response is crucial for signal specificity.
True or False: Signal transduction must be terminated once initiated.
True
This is essential for maintaining cellular homeostasis.
What is the intrinsic enzymatic activity of receptor tyrosine kinases?
They have intrinsic kinase activity that phosphorylates tyrosine residues
This is a characteristic feature of RTKs.
What is the significance of signaling networks in cell signaling?
They lead to cross-talk and integration of multiple signaling pathways
This enhances the complexity and specificity of cellular responses.
How does the reversibility of phosphorylation contribute to the dynamic nature of signal transduction?
- a protein that is activated by a protein kinase is inactivated by a protein phosphatase
- effects of the signals can’t last forever
- more signals must be received for the cellular response to continue
What are RTKs?
- receptor tyrosine kinases
- active as dimers
- trans-phosphorylate when a ligand is bound
- phosphorylated tyrosines in the receptor tail assemble an intracellular signalling complex
- inactivated by de-phosphorylation and receptor internalisation
Signalling in RTKs
Phospho-tyrosine residues create a specific binding (docking) site to allow association & activation of downstream signalling proteins in receptor tails
= generates a signalling complex
RAS activation
RAS is a monomeric G protein that acts as a molecular switch downstream of RTK at the plasma membrane
RAS-GEF = a guanine exchange factor that exchanges GDP for GTP —> turns RAS on = SOS is the GEF
RAS-GAP = a GTPase activating protein that is used for GTP hydrolysis —> turns RAS off = GAP
Structure of GRB2
Contains one SH2 domain and one SH3 domain
SH2 domain binds to phospho-tyrosine residues
SH3 domain interacts with proline rich sequences = recruits SOS to the cell membrane
What is the MAPK pathway?
- RTKs activate the monomeric G protein RAS
- RAS does not bind directly to RTKs
- RAS activates the MAPK pathway
- The MAPK cascade regulates protein activity and gene expression
What does MAPK target?
- phosphorylation of cytoskeletal proteins = altered cell shape
- phosphorylation of enzymes = altered cell metabolism and altered response to stimuli
- phosphorylation of gene regulatory proteins = altered expression of many genes involved in cell survival, proliferation, migration and differentiation
What is PI3K?
Phosphatidylinositol-3-kinase
- a heterodimeric lipid kinase
- the regulatory subunit has a SH2 domain (can interact with phosphorylated tyrosine residues)
- the catalytic subunit has an ATP binding site and dual specificity
Principles of signal transduction
- different receptors initiate different signalling cascades
- different cell types transduce signals differentially even when the same receptor is activated
- signal transduction allows signal amplification
- signal transduction must be terminated
