Lecture 1: Introduction to Module Flashcards
Why is cell signalling important?
It is important because without it, we would not be able to progress past single cell organisms. It allows for cell differentiation, and compromised cell signalling will lead to disease.
Cell to cell communication can be categorised in a number of different ways, name a few of these methods.
Paracrine
Endocrine
Cell-cell contact signalling
What is the difference between paracrine and endocrine signalling?
Endocrine uses the circulatory system to exert its effects.
Paracrine signals diffuse a short distance to nearby cells.
What are the 2 main mechanisms by which a molecule can elicit a response from a cell?
A rapid, non-genomic response:
- A neutrophil releasing contents of granules when PRRs detect PAMPs
A delayed, genomic response:
- Testosterone, after binding to androgen receptor, turns it into a transcription factor that will travel to nucleus and begin exerting effects.
What properties do hormone receptors share?
They are specific to certain hormones.
The hormones can be inside or outside of a cell (on plasma membrane or in the cytosol).
Levels of receptors are not static (can be up-regulated or down-regulated).
LOOK UP GREEN DYE SOMETHING TO DO WITH JELLYFISH?
GFP - Green Fluorescent Protein
Used for many processes.
An example would be tracking gene function by attaching GFP to gene of interest and observe glow in cells.
What is signal transduction?
Signal transduction is the process of converting a signal from a receptor to an effect inside the target cell.
Where are the receptors for hydrophilic hormones located?
They are located on the plasma membrane of the cell, as signalling molecules are poorly soluble in lipids.
What do signal transduction pathways rely on?
A receptor that is intrinsically enzymatic.
A cytoplasmic JAK Kinase enzyme.
G-coupled protein receptors.
What happens when a hydrophilic hormone binds to a receptor?
It causes a conformational change, resulting in the activation of a signal transduction pathway.
Describe what happens in a receptor tyrosine kinase pathway.
The receptor binds to its ligand and its intrinsic tyrosine kinase activity activates cytoplasmic proteins by phosphorylation.
Discuss the relationship between tyrosine kinase and disease.
BCR-ABL in chronic myeloid leukaemia.
ABL-1 is a protein tyrosine kinase that helps regulate many cell functions such as cell division, cell differentiation, etc.
ABL-1 normally has a protein cap on to inhibit activity, but when the ABL-1 gene is translocated from the end of chromosome 9 to the end of chromosome 22 (where BCR gene is located), this translocation leaves BCR and ABL next to each other.
The new BCR-ABL does not have the protein cap that inhibits ABL function and therefore is constantly stimulating cell division.
BCR also has threonine-serine kinase activity, exacerbating the issue.
95% of all CML cases have this gene.
Describe what happens in JAK kinase pathways.
Receptor monomers embedded in the membrane dimerise when they bind a ligand. This increases affinity for JAK kinases, and each monomer will bind one. Both kinases phosphorylate each other and tyrosine residues on the dimer. STAT molecules bind to phosphate groups on the dimer and JAK will phosphorylate these too. Upon phosphorylation, two STAT molecules will form a dimer (2 phosphate, 2 STAT), that will influence transcription factors.
What is the history of the name JAK?
JAK kinase stands for Janus Kinase.
Janus was a roman god that had two faces, one that looks into the past and one into the future.
Named because it looked like it had two faces.
Original name was because so many kinases were being found all of them were called Just Another Kinase.
What are the 4 important JAK proteins in humans?
JAK1
JAK2
JAK3
TYK2
All JAK proteins play roles in various cell functions. JAK 1 and 2 play a role in IFN-y (IFN-2) signalling. Whereas JAK 3 and 4 play more of a role in IFN type 1 signalling.
