Week 4 - Signal Transduction and Cancer Flashcards
Name the four main forms of intercellular signalling.
Contact Dependent
Paracrine
Autocrine
Endocrine
Describe contact dependent signalling
Physical connection between signalling cell and adjacent target cell through membrane-attached signal proteins
Describe Paracrine signalling
Signalling cell release substrate (signalling protein) which binds to receptor on membrane of local target cell(s).
Describe Autocrine signalling
Signalling cell and targeting cell = same cell
The cell releases substrate extracellularly which then binds to the receptor on the cell’s surface.
Describe Endocrine signalling
Endocrine cell = Signalling cell
Release of hormones that travel through the bloodstream to the target cell.
What is the role of a kinase?
A kinase is an enzyme that catalyses the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates.
Name 4 different types of post-translational modifications.
Acetylation
Methylation
Lipid conjugation
Ubiquitination
How is a signalling pathway inactivated?
Through inactivating enzymes such as: Phosphatases and deacetylases. (Opposites to the post-translational modifications)
Give a reason as to why a ligand can cause a different response in different cell types.
- One ligand can bind different receptors
2. The same receptor utilises different intracellular signalling molecules to transmit the signal
Give 3 types of transmembrane receptors and a example of each.
- Ion channels
- G protein-coupled (e.g. adrenergic receptors)
- Tyrosine kinases (e.g. PDGF, EGF)
- Tyrosine kinase-associated (e.g. most cytokines)
- Ser/Thr kinase (e.g. TGFβ)
- Tyrosine phosphatase (e.g. EPO)
- Proteolysis-linked (e.g. Notch)
Give 2 example of transcription factors and their triggers.
TF –> Trigger:
- NF-kB - Immune stress
- CREB - Cyclic AMP
- Oestrogen Receptor - Oestrogen
- ISGF3 - Interferon
What is the process of G-Couple Receptor activation?
- Ligand binds to active site on extracellular portion of receptor
- Induction of conformational change
- Recruitment of Heterotrimeric G-Protein (GDP+G(alpha)+G(gamma)+G(beta))
- GDP/GTP Exchange
- G protein sub-unit dissociation from receptor
- G(alpha)+GTP dissociation - continued downstream activity.
State 4 actions of protein kinase A.
- Glycogen breakdown
- Ion channel regulation
- Transcriptional activation (CREB)
- Ca2+ influx/ Muscle contraction
- Cytoskeletal rearrangements
Describe the process in which protein kinase A is formed.
- Ligand binds to active site on extracellular portion of receptor
- Induction of conformational change
- Recruitment of Heterotrimeric G-Protein (GDP+G(alpha)+G(gamma)+G(beta))
- GDP/GTP Exchange
- G protein sub-unit dissociation from receptor
- G(alpha)+GTP dissociation - continued downstream activity.
- G(alpha)+GTP bind to Adenylate Cyclase
- Adenylate Cyclase converts ATP to cAMP
- cAMP activate Protein Kinase A
Describe the Gq/11 pathway.
- Ligand binds to active site on extracellular portion of receptor
- Induction of conformational change
- Recruitment of Heterotrimeric G-Protein (GDP+G(alpha)+G(gamma)+G(beta))
- GDP/GTP Exchange
- G protein sub-unit dissociation from receptor
- G(alpha)+GTP dissociation - continued downstream activity.
- G(alpha)+GTP bind to PLC
- Hydrolysis of PIP2 to IP3 and DAG
- DAG binds to PKC
- IP3 binds to Sarcoplasmic Reticulum - Ca2+ release
- Ca2+ activates Calmodulin
- This activates Calmodulin Dependent enzymes which go on to form subtrates such as NF-AT
