Signalling 1 Flashcards
list three types (bi)chemical signalling molecules
Hormones
Neurotransmitter
Growth factors
What are two classifications of signalling molecules?
Distance they act over
Chemical structure
Name some lipid based hormones
testosterone, cortisol, prostaglandins
what are are eicosanoid hormones derived from?
Lipids
What are steroid hormones derived from?
Cholesterol
Give 2 examples of protein hormones?
Growth factor, insulin
What are 4 ranges a signalling molecule can act? and what is each way called
Neighbouring/adjacent cells (juxtacrine -via cell to cell contact) Nearby cells (paracrine - via diffusion) Same cell (autocrine) Over whole body (endocrine)
What are the 3 steps in signal transduction?
Reception/detection of signal
Transduction (relaying signal from receptor to part of cell where response is initiated)
Response
List 7 responses a cell can have in response to a signal
Divide Differentiate Migrate Change shape Increase/decrease cell activity Produce new proteins Transcribe new Genes Release hormones Grow Die
Describe the two types of receptors and give examples
For Hydrophilic signalling molecules = cell surface receptors e.g. for insulin, adrenaline, some neurotransmitters, most peptide hormones
For Hydrophobic (lipophilic) signalling molecules = intracellular receptors e.g. for steroid hormones (oestrogen, testosterone), nitric oxide
Describe how hydrophobic signalling molecules work in a cell
E.g. oestrogen, testosterone.
Signalling molecules enters cell and binds to intercellular rectory proteins. Hormone receptor complex forms which acts as a transcription factor. It binds to DNA and alters gene expression.
List the 3 main types of cell surface receptors and give an example of each
Ion channel linked e.g. glutamate neurotransmitter
G-protein coupled e.g. adrenaline, NT: serotonin
Enzyme linked e.g. RTK
Describe how an ion channel linked receptor works
Signalling molecule binds to receptor (receptor can be ion channel or coupled to an ion channel)
Ion channel opens and ions flow either in or out of the cell along a concentration gradient
Change in electrical properties of the cell occurs
Briefly describe the structure of a G protein coupled receptor
It is a large heterotrimeric, transmembrane protein
Describe and draw how a G protein couple director works
Signalling molecule binds to receptor. The G protein which is coupled to the receptor undergoes a conformational change and is active activated. The activated G protein goes off and activates an enzyme. The enzyme transmits the signal in the cell
In enzyme linked receptors where can the enzymatic activity be?
Enzymatic activity can either be in the catalytic domain (where catalysed reaction occurs) or it can be coupled to an independent enzyme
What type of molecules act as Ligands to receptor tyrosine kinases?
Growth factors
what is the role of RTK?
It is an enzyme that adds a phosphate group to the amino acid tyrosine in a target protein
Describe how a ligand acts on RTK
Ligand is often a dimer (2 monomers joined together) and as it binds to RTK, the receptor dimerises (2 monomers come together).
The kinase activity of the cytoplasmic domain of RTK is activated and it autophosphorylates.
Cytoplasmic domain has tyrosine resides that can be phosphorylated. Cross phosphorylation of the different monomers of the dimer occurs and it causes shape change due to addition of phosphate group.
Intracellular Proteins bind to the phospho-tyrosine docking sites and the signal is transmitted
what are the 2 main methods of transduction of a signal?
Enzyme cascades
Second messengers
Give an example of an enzyme cascade and what ligand is it used by
MAP Kinase Cascade, used by growth factors such as EGF
Describe the MAP kinase cascade
Ligand (e.g. EGF) binds to its receptor (EGFR) and the receptor TK becomes phosphorylated.
Relay proteins bind to the phosphorylated form of receptor TK and activate RAS.
RAS mediates signals from the receptor and docked proteins and activates a MAP kinase cascade.
RAS activates Raf, which activates and phosphorylates MEK. MEK activates and phosphorylates ERK.
ERK can alter the transcription of target genes
What is a second messenger? Give 2 examples
A small molecule produced in large amounts inside a cell after receptor activation. It coordinates cell response. E.g. calcium ions and cAMP
describe an example of when second messengers are used
Adrenaline activates G protein coupled receptor. Activated G protein goes on and activates enzyme adenylyl cyclase. Adenylyl cyclase produces cAMP, which activates protein Kinase A. Protein Kinase A goes onto phosphorylate target proteins.
From here, PKA can flow one of 2 pathways
It can either:
Activate phosphorylase kinase, which phosphorylates and activates and enzyme (PHOSPHORYLASE), which breaks down glycogen to release glucose into bloodstream
OR
Inhibit an enzyme called glycogen synthase which produces glycogen from glucose
In cancer what change occurs to the GF/RTK pathway? What treatment can be used?
The RTK pathway is usually overactive causing over expression or a mutation to occur.
Treatment: antibodies or kinase inhibitors
what functions as the off switch in the adrenaline and cAMP pathway
Phosphodiesterase: breaks down cAMP which stops the system and switches the signal off
give 2 examples of peptide hormone signalling molecules
growth hormone
Insulin
give 2 examples of peptide growth factor signalling molecules
Epidermal growth factor
Erythropoietin
