Cell Signalling Flashcards
What are the three cycles of cell signalling?
- Ligand-receptor interaction
- Signal transduction
- Cellular response
What is ligand-receptor interaction ?
A process by which a specific receptor protein on or in target cell detects the signal
This occurs during complementary binding of the ligand (signalling molecule) to the specific site on receptor
What is a ligand ?
Molecules that specifically bind to another molecule
What are the characteristics of ligands that bind to cell surface receptors ?
Water soluble
Generally too large to pass freely through plasma membrane
What are some examples of cell surface receptors ?
G-protein linked receptor
Receptor tyrosine kinase
Ion channel receptor
What are the two effects of ligand-receptor interaction ?
- Ligand binding generally causes receptor protein to undergo conformational change, which in many receptors would directly activates the receptor, enabling it to bind with other cellular molecules
- For other kinds of receptors, the immediate effect of ligand binding is to cause the aggregation of two or more receptor molecules, which leads to further molecular events inside the cell
What is signal transduction ?
A process by which extra cellular signals are converted into intracellular signals to generate specific cellular responses
Usually a multi step pathway, involving a series of interactions between relay molecules that operate in sequence
How is signal transduced ?
- Phosphorylation (and dephosphorylation) of relay proteins which changes conformation of these proteins and thus results in their activation (and deactivation)
- Production of small non-protein molecules and ions known as second messengers to relay the signal inside of the cell
What does upstream and downstream mean, relative to a particular molecule of interest ?
Upstream - molecules and events that come earlier in the relay chain
Downstream - molecules and events that come later
What is a kinase ?
An enzyme which catalyses the addition of phosphate groups from ATP to protein
What are phosphatases ?
Enzymes that can catalyse removal of phosphate groups from the proteins, making them inactive which ends signal transduction thus making proteins in the pathway available for reuse
What is a phosphorylation cascade ?
Where a series of different protein kinases arranged in a pathway are phosphorylated sequentially
What are second messengers ?
Small, non-protein, water-soluble molecules or ions
Able to spread throughout the cell by diffusion
What do second messengers do?
Molecules that relay signals received at receptors on the cell surface to target molecules in the cytoplasm and/or nucleus
They also serve to greatly amplify the strength of the signal
What are the widely used second messengers?
cAMP
Calcium ions
What is the significance of the multistep pathway in cell signalling ?
Amplification of signal
What is a phosphorylation cascade ?
An active kinase catalysing the phosphorylation of many kinases, thus activating them. Each of these active kinases go on to phosphorylate and activate many kinases in subsequent steps
At which point in the signal transduction pathway does the cell’s specific response occur ?
The end of the signal transduction pathway
What are the two types of cellular responses ?
Cytoplasmic responses
Nuclear responses
What is involved in cytoplasmic responses ?
Mainly changes in activity of enzyme and proteins in cytoplasm leading to changes in cell metabolism
What are nuclear responses ?
When specific genes coding for synthesis of enzymes or other proteins are switched on or off ( in nucleus )
Why can two cells respond differently to the same signal ?
Due to difference in one or more of the proteins that handle and respond to the signal
What does the response of a particular cell to a signal depend on ?
On the specific collection of signal receptor proteins, relays proteins and functional proteins need to carry out the response
What are scaffolding proteins ?
Large relay proteins to which several other relay proteins are simultaneously attached
What is the importance of scaffolding proteins ?
Physical arrangement facilitates signal transduction of these molecules by keeping them close together so that transduction pathway reaction can be organised closely together and in order, increasing speed of pathway
When do relay proteins participate in different signalling pathways ?
In different cell types
In the same cell at different times or conditions
What is the key to a cell being able to continuously being receptive to regulation by signals ?
The reversibility of the changes that the signal produce
What enzyme is involved in conversion of cAMP back into AMP ?
Enz phosphodiesterase
What enzyme inactivates pkA ?
Enzyme phosphatases through removing the attached phosphates
What is homeostasis ?
The mechanism by which the internal environment of an organism is kept constant
What is the normal blood glucose level in humans ?
80-120 mg glucose / 100 cm3 of blood
What is the blood glucose level after a meal ?
150 mg glucose/ 100cm3 of blood
What is the blood glucose level after exercise ?
70 mg glucose / 100cm3 blood
What are the two hormones that control blood glucose levels ?
Insulin
Glucagon
How are changes in blood glucose levels detected ?
Blood flows to pancreas and the alpha and beta cells of the islets of langerhans detect the changes
What detects high blood glucose above norma levels ?
ß cells of the islets of langerhans
What detects Low blood glucose below normal levels ?
Alpha cells of the islets of langerhans
When blood glucose concentration is higher than normal, which hormones is secreted ?
Insulin
When blood glucose concentration is lower than normal, what hormone is secreted?
Glucagon
Which organs are part of response to insulin ?
Liver and muscle
Which organs are part of response to glucagon ?
Liver
When does type I diabetes occur ? How to overcome ?
When the pancreas does not produce enough insulin, patients must take insulin shots
What is type II diabetes ? How to overcome ?
When body is resistant to insulin in the blood
Regulated through increased exercise, controlled diet and other medications
What is the receptor for insulin ?
Receptor tyrosine kinase
What are RTKs?
Transmembrane receptors which span across the entire plasma membrane
What does the part of the RTK which extend into the cytoplasm function as ?
Tyrosine kinase - catalyses transfer of phosphate group from ATP specifically to AA tyrosine on substrate protein
What is special about the insulin receptor RTK compared to other RTKs ?
Insulin receptor RTK exists in inactive covalent disulfide-linked dimer in the absence of a ligand (already in dimerised formed before activation) while for most RTKs, each receptor exists as individual polypeptide in its inactive state
What happens when insulin binds to RTK ?
Ligand binding causes conformation change to receptor, activating it
Where does insulin bind to on RTK ?
Extracellular ligand binding site
What happens after insulin activates RTK ?
The tyrosine kinase region at the intracellular region of each polypeptide is activated
Cross phosphorylation occurs
What is cross phosphorylation in RTK ?
When each tyrosine kinase of each polypeptide of the RTK phosphorylated tyrosine residues on the tail of the other polypeptide
What does activation of RTK result in (signalling pathway) ?
Specific relay proteins recognise the activated RTK, bind to specific phosphorylated tyrosine reside and undergoes conformational change that activates the relay proteins
What are the four effects of insulin on target cells ?
- Facilitates transport of glucose into cells by increasing the number of glucose carriers on cell membranes
- Activation of glucokinase
- Stimulate glycogenesis
- Inhibits glycogenolysis
How does insulin result in increase in number of glucose carriers on cell membrane ?
Signal transduction pathway causes vesicles in the cytoplasm that contain glucose carriers to move and fuse to the cell membrane
What does glucokinase do ?
Attach phosphate group to glucose molecule
Why does insulin signal for activation of glucokinase ?
Liver cells are impermeable to phosphorylated glucose, thus by phosphorylating glucose it becomes trapped within cell and steep concentration gradient is maintained to continually take in glucose by facilitated diffusion
What is glycogenesis ?
Glycogen synthesis from glucose
Which enzyme is involved in glycogenesis ?
Glycogen synthetase - polymerises phosphorylated glucose into glycogen in liver cells
What is glycogenolysis ?
Breakdown of glycogen to glucose
Which enzyme is involved in inhibition of glycogenolysis (insulin) ?
Glycogen phosphorylase is inhibited - enz which catalyses breakdown of glycogen to glucose
What are G-protein linked receptors ?
Membrane receptors which consists of seven a-helixes spanning the membrane
Specific loops between the helices form specific binding sites for attachment of extracellular ligand binding and intracellular G-protein
What happens after G-protein coupled receptor is activated ? (Signal transduction)
Cytoplasmic side of the receptor binds to inactive G-protein causing GTP to displace GDP resulting in G-protein activation
What does the G-protein do after activation ?
It dissociates from the receptor, moves along the membrane and binds to and activates an enzyme on the cytoplasmic side of the membrane
What enzyme does activated G-protein activate ?
Adenylyl cyclase
What does activated adenylyl cyclase do ?
Catalyses conversion of many ATP into many cAMP molecules
What do cAMP do as part of signal pathway for glucagon ?
Serve as second messengers which bind to and activate protein kinase A
What are the three effects of glucagon on target cells ?
- Results in glycogenolysis
- Prevent formation of glycogen from glucose
- Stimulate gluconeogenesis
Which enzyme is involved in glycogenolysis ?
Glycogen phosphorylase - catalyse breakdown of glycogen
What is gluconeogenesis ?
Generation of glucose from non-carbohydrate carbon substrates in the liver
