Signalling 1 Flashcards
What is cell signalling?
Cell communication: the process of cells constantly sensing, intergrating and responding to various different signals in their environment. This allos normal function of both individual cells and tissue/organ/ body coordination
List examples of singals in cell’s environment:
Nutritional status (e.g. glucose, amino acids)
Oxygen supply
Temperature
Pathogens
Other cells producing: hormones, growth factors, pro-apoptotic factors
List example of cell responses to environmental signals:
Die
Grow
Divide
Differentiate
Migrate
Change shape
Increase/ decrease activity
Produce new proteins
Transcribe new genes
Release hormones
Examples of when cell signalling is important
Coordinating development: morphogens in embryological development, failures can lead to diseases such as cyclopia
To maintain normal physiological functions: such as controlling blood glucose loeves with insulin and glucagon, diabetes occurs when this goes wrong
2 examples of abnormal signalling causing disease:
Diabetes - insufficient insulin production, reduced responsiveness to insulin in target cells
Cancer - gene mutations causing uncontrolled cell division
Examples of drugs working by targeting signalling:
Herceptin - used for breast cancers, targets cell surface growth factor receptor (HER2)
Salbutamol - asthma reliever, B2 cell surface receptor
Gleevec - targets intracellular protein tyrosine kinase (bcr-abl)
Avastin - targets VEGF which signals for angiongenesis, helps prevent tumour gaining blood supply
List and give examples of the 3 different types of signal:
- Physical - e.g. pressure, temperature
- Electrical - nerve cells, ions
- Biochemical - e.g. hormones, growth factors, neurotransmitters
What are the 2 ways of classifying biochemical signals?
Chemical structure
Range of action (distance)
What are the 3 chemical types of hormones?
- Amino-acid derivatives: modified amino acids (adrenaline), peptide hormones (oxytocin), protein hormones (insulin, growth hormone)
- Steroid hormones: derived from cholesterol (testosterone, cortisol)
- Eicosanoids: derived from lipids (prostaglandins)
What are the terms for classifying signals based on range of action?
Endocrine (via blood) - long distance
Paracrine - to nearby cells by diffusion
Juxtacrine - to neighboring cells via cell to cell contact
Autocrine - same cell
What are the 3 common stages for all signalling in cells?
Individual cells must:
1. DETECT a signal/ stimulus
2. TRANSDUCE the signal from site of detection to part of cell that will respond
3. RESPOND - must be coordinated with responses to other signals and with responses of other cells
What are the 2 types of receptors used for signal detection?
Intracellular receptors and cell surface receptors
Why are intracellular receptors used?
Hydrophic signalling molecules such as steroid hormones or NO can diffuse across plasma membrane and bind directly to them.
Mode of action of steroid hormones causing a reponse:
- Diffuse directly across plasma membrane
- Bind to intracellular receptor protein
- Hormone-receptor complex acts as transcription facor by binding to DNA and altering gene expression
When are cell surface receptors used?
Water soluble/ hydrophilic molecules such as insulin or adrenaline are unable to diffuse across plasma membrane so need to bind to cell surface receptor
List and describe the 3 main types of cell surface receptor
- Ion-channel linked: signal binds to receptor of ion channel which causes it to open, allowing ions to flow into cell changing the cells electrical properties
- G-protein-linked/ coupled receptors: signalling molecules bind to receptor, activating G protein which then activates enzymes passing signal into the cell
- Enzyme linked receptor: singal binds to inactive receptors, brings 2 parts of receptor together activiating its enzyme activity
Give examples of the 3 types of cell surface receptors:
Ion-channel linked: glutamate neurotransmitter
G-protein-linked: adrenaline, serotonin, glucagon recptors
Enzyme linked: receptor tyronase kinases such as EGF (adds phosphate to alter protein function
Two main methods of signal transduction and amplification:
Enzyme cascades
Second messengers
Explain an example of an enzyme cascade:
The MAPK cascade
- Activated in response to Growth Factor RTK activation (e.g. EGF)
- Relay proteins Grb/ Sos activate RAS (a proto-oncogene, commonly mutated in cancer)
- Ras activates a MAP kinase cascade which amplifies signal: one enzyme activating another in a chain reaction, each time the next enzyme is activated the signal is activated as each molecule can activate many other molecules.
There are multiple MAPK cascades which respond to different receptors to produce different cellular responses.
Define a second messenger:
Small molecule produced in large amounts inside cell after receptor activation that coordinates cell response (e.g. cAMP)
Demonstrate the mechanism of secondary messengers using adrenaline as an example
- Adrenaline binds to adrenaline receptors (a form of GPCRs),
- These activate G protein, which activates adenylyl cyclase
- This produces cAMP (secondary messenger)
- cAMP activates PKA (a protein kinase) which directly/ indirectly leads to phosphorylation of lots of different target proteins
- Enzymes are used to make cAMP so causes amplification as 1 adrenaline can cause production of many cAMP molecules
General rule of thumb for transduction:
RTKs activate MAPK cascades
GPCRs use secondary messengers
What are some of the possible molecular level responses?
Gene expression
Protein activity (phosphorylation altering metabolic enzyme activity)
Protein binding (inhibitor/ activator proteins, or to DNA)
Protein localisation (transcription factor activated by moving from cytosol to nucleus)
How can one signal cause multiple responses? Give an example:
One receptor is able to activate multiple signalling pathways.
One signalling pathway can activate mutliple different responses
Example:
EGF receptor can result in survival, proliferation or invasion
How is specifity in signalling achieved?
Cells response to signal depends on types/ levels of receptors, transducers and effectors expressed in that cell. Although genes are the same the expression varies from cell to cell so the same hormone can have a different effect on different tissues
Give an example of a hormone which can cause different responses from different cells:
How does it do this:
Different effects of Adrenaline:
-Glucose release from skeletal muscle and liver
-Increased heart rate and force
-Vasodilation of some blood vessels but vasoconstriction of others
-Bronchodilation
Mechanism for different outcomes:
- Binds to multiple different GPCRs
- Multiple different G proteins activated
- Multiple second messengers and protein kinase transducers produced
- Multiple target proteins
Give 2 examples of pharmocology utilising cell signalling:
Salbutamol (asthma drug) - an agonist (like adrenaline) causes bronchodilation
Betablockers (blood pressure) - antagonist to adrenaline (oppose it) which decreases heart rate and force which lowers blood pressure
