Hormones and cell signalling Flashcards
What is autocrine signalling?
One cell recieves a weak signal and then all the adjacent cells tell each other to make a strong signal for the tissue.
Why is autocrine signalling good?
This will encourage groups of identical cells to make the same developmental decisions. This is sometimes referred to as the community effect that is observed in early development, during which a group of identical cells can respond to a differentiation inducing signal but a single isolated cell of the same type can not.
What are the differences between water and lipid soluble hormones?
Lipid soluble
Transported in blood by carrier proteins
Diffuse through plasma membrane
Alters expression of genes at level of nucleus
Water soluble
Easily travel in blood
Bind to receptors on the surface of the cell
Results in series of intracellular events
Most signal molecules are hydrophillic, what does this mean for the cell?
They are unable to cross the plasma membrane directly; instead, they bind to cell-surface receptors, which in turn generate one or more signals inside the target cell.
Some small signal molecules diffuse across the plasma membrane, what do they bind to?
They bind to receptors inside the target cell either in the cytosol or in the nucleus
Many of these small signal molecules are hydrophobic and nearly insoluble in aqueous solutions, so how are they transported?
They are therefore transported in the bloodstream and other extracellular fluids after binding to carrier proteins, from which they dissociate before entering the target cell.
Are growth factors water or lipid soluble?
Water
Are steroids, thyroid hormone and vitamins A and D water or lipid soluble?
Lipid
What happens when a hormone binds to its nuclear receptor?
The hormone and receptor meet, the receptor is activated, the activated receptor binds to the DNA and regulates the transcription of specific target genes. Each hormone-nuclear receptor complex regulates a specific set of genes in a cell type specific manner
What is the general structure of a nuclear receptor?
At the NH3 end they have a transcription activating end, in the middle they have a DNA binding domain and a hormone binding domain at the COOH end.
When activated the nuclear receptor recruits ………………………..
additional coactivator proteins
When inactive the nuclear receptor is bound to …………………….. but the binding of a ligand causes…
inhibitory proteins
the ligand-binding domain of the receptor to clamp shut around the ligand, the inhibitory proteins to dissociate, and coactivator proteins to bind to the receptor’s transcription-activating domain, thereby increasing gene transcription.
What possible intracellular signal transduction pathways can be activated by membrane bound receptors?
Adenyl cyclase (cyclic AMP) Guanyl cyclase (cyclic GMP) Phospholipase C, IP3, and DAG Tyrosine kinase Ion channels
ACTH, ADH, FSH, LH and TSH activate which intracellular pathway?
Adenyl cyclase
TRH and GnRH activate which intracellular pathway?
Phospholipase C
Insulin, prolactin, growth hormone and IGF activate which intracellular pathway?
Tyrosine kinase
What are the three components of membrane receptor?
External domain (binds signal) Transmembrane domain Cytoplasmic/intracellular domain
What change is made to the receptor when it binds to a ligand?
Cytoplasmic domain undergoes conformational change
This usually involves the activation of dormant enzymatic activity, often a protein kinase. The receptor then phosporylates intracellular proteins and hence we have signal transduction.
Cytokines =
growth factors = polypeptides that promote cell growth and/or proliferation
What happens when a growth factor binds to a receptor?
Ligand binding activates tyrosine kinase.
This initiates a signal that is propagated through the cell by a process of phosphorylation. This can occur in a number of ways the main one being through a small nucleotide binding protein called Ras.
How does the Ras protein work?
This is a membrane associated protein which cycles between active and inactive states and this in turn is regulated by GTPase activating proteins or GAP.
This ultimately activates transcription factors and hence the production of growth response genes
What does termination of the signal depend on?
Response fades once signal withdrawn
Depends on rate of destruction or removal of molecules that the signal affects
What is the half life of a signalling molecule?
Time taken for the concentration of a signalling molecule to fall by half.
Transient signals may have long lasting effects
Many intracellular proteins have short half lives
Different cell types are specialized to respond to acetylcholine in different ways, how?
For these cell types, acetylcholine binds to similar receptor proteins, but the intracellular signals produced are interpreted differently in cells specialized for different functions.
Name the 4 most important water soluble hormone receptors?
- Ion-channel-linked receptors
- G-Protein linked receptor
- Tyrosine kinase-linked receptor
- Receptors with intrinsic enzymatic activity
How do Ion-channel-linked receptors work?
The Signal molecule (neurotransmitter) binds to receptor and this opens (or closes) an ion channel. Ions move into cell passively by diffusion and the Excitability of post-synaptic cell altered
Second messengers can be…
Small intracellular mediators like:
cAMP, cGMP (water soluble)
Ca2+ released from intracellular calcium stores
diacylglycerol (DAG) which is lipid soluble
Which could then go and relay the signal to larger intracellular proteins
The larger intracellular proteins that the second messengers go to could be…
Scaffolds Relays Adaptors Amplifiers Modulators And this allows them to integrate many different signals from different signalling molecules into perhaps the same effect
What enzymes are responsible for protein phosphorylation?
enzymes called kinases
What enzymes are responsible for dephosphorylation?
enzymes called phosphoprotein phosphatase
What is the G protein receptor/ 7 transmembrane receptor?
Single polypeptide chain with a central hydrophobic region that spans the plasma membrane 7 times
The polypeptide has 7 loops in order to form the bottom loop that interacts with the G protein
Give an example of a G protein receptor
muscarinic acetycholine receptor
Give an example of an ion channel receptor
nicotinic acetylcholine receptor
What is the G protein?
Guanine-nucleotide binding protein: A signal transducing protein
How does the G protein receptor work?
A signal molecule binds to the receptor and the receptor recruits the G protein to the intracellular loop
Then GTP replaced GDP and this causes which causes our G protein (which is composed of 3 different proteins to dissociate into two units:
An activated alpha unit
A Beta gamma unit
So now from one signalling molecule we have two activated pathways
What are the two types of enzyme linked receptor?
Receptors with intrinsic enzymatic activity: Enzymes that within their own intracellular domain have intrinsic tyrosine kinase activity, typically dimeric
Receptors with associated enzymatic activity: Receptors that recruit receptor associated tyrosine kinases
How do insulin receptors work?
The receptor is linked to TK and Tyrosine kinase not only acts my adding a phosphate but it also changes the neutral charge of the AA in the protein to a negative so anything positive can stick to it, so is a receptor is phosphorylated it then acts like a docking station for the intracellular signalling proteins
This sets off the Phosphoinositide 3-kinase (PI 3-kinase) pathway
What does the Ras pathway initiate?
It activates transcription factors and gene activation which could result in cell replication
What do Receptor tyrosine kinases do?
Phophorylate tyrosines on intracellular signalling molecules
What do Tyrosine-kinase-associated receptors do?
Associate with intracellular proteins with tyrosine kinase activity
What do Receptor-like tyrosine phosphatases do?
Remove phosphate groups from tyrosine on intracellular proteins
What do Receptor serine/threonine kinases do?
Phosphorylate serines or threonines on regulatory proteins
