Kinases Flashcards
What are kinases?
Kinases are enzymes which phosphorylate protein molecules. They are key parts of signalling pathways in cells.
What is the relationship between kinase and phosphetase activity? Why is this seen?
Phosphatase activity is usually higher than kinase activity to control the activity of kinases and prevent signals being sent incorrectly; with them only being sent when kinase activity is induced.
What is the opposite of a kinase?
The ‘opposite’ of a kinase is a phosphatase, which removes phosphate groups from protein molecules.
What are tyrosine kinases?
Tyrosine kinases are tails portions of receptors which are located within the cell; two of these receptors are often found next to each other.
What happens when a receptor tyrosine kinase is activated?
When the receptor is activated, the tyrosine kinases phosphorylate each other, his is known as transphosphorylation. This activates the receptor and turns on downstream signalling.
When a receptor tyrosine kinase is activated, what happens?
The activated receptor goes on to recruit other proteins (e.g. adaptors such as Grb and SOS). These recruit other proteins and activate them (e.g. kinases). The kinases recruited phosphorylate downstream targets, activating them.
With respect to receptor tyrosine kinases, what does phosphetase activity do?
Phosphatase activity acts to dephosphorylate the receptors and prevent them being activated unless needed.
Give some potential targets in the receptor tyrosine kinase pathway.
- Antagonism of ligand binding/dimerization.
- Antagonism of ATP binding.
- Prevention of transphosphorylation.
- Prevention of recruitment of adaptors (relay proteins).
What is the MAPK pathway?
The MAPK pathway is an important signalling pathway, especially in tumour growth.
Give some examples of the functions that the MAPK pathway is involved in.
- Proliferation.
- Cell cycle.
- Differentiation.
- Transformation.
- Survival (apoptosis).
- Cytoskeleton.
- Adhesion.
- Motility.
Mutations in the cell cycle are common in cancer, these are commonly mutations where?
Mutations in control of the cell cycle are common in cancer, these are most commonly mutations in the checkpoint systems in place to prevent the proliferation of damaged or mutated cells (usually based on DNA).
Intracellular inhibitors of kinases are small molecule inhibitors of the EGFR TK domain, most of them fall under which category?
Anilinoquinazolines.
Give examples of intracellular inhibitors of kinases that are in use.
- Gefitinib (Iressa) (AstraZeneca).
* Erlotonib /Tarceva (OSI/Genetech).
