Topic 2:Principles of Protein Signalling Flashcards
Principles of Protein Signalling
extracelluar response to cellular response
1) synthesis of signalling molecule
2) release of the molecule by exocytosis
3) movement of molecules to target cell
4) the molecules act as ligands to bind to the protein receptor on the target cell
5) binding causes a conformational change in the receptor
6) that initiates intracellular pathways like metabolism or gene expression
7) the receptor then gets deactivated and the ligand is removed
What are the 5 types of ways signalling molecules can travel?
- autocrine
- paracrine
- juxtacrine (contact depending)
- endocrine
- synaptic
What is paracrine signalling?
when the signalling molecules travel a short distance to the target cells
- local
What is autocrine signalling?
when the signalling molecules come within the cell and target receptors on it’s own surface
- local
What is endocrine signalling?
when the signalling molecules travel through the bloodstream to its target cell
- the slowest way
- long distance
what is synaptic signalling?
is when the signalling molecules (called neurotransmitters) are released by a neuron
- long distance
- very fast
what is juxtacrine (contact signalling)?
when the signalling molecule is a membrane bound molecule and the target receptor is directly next to it
Factors that affect the speed of an extracellular response
- different signalling molecules have different speeds
- the same receptor may have different intracellular pathways
what is the relation between growth and differentiation
there is no relation
one can be done without the other
What are the type of cell responses to extracellular signals
- growth+divide
- survive
- differentiate
- die
examples of a ways signal and response times vary
- sensitivity
- persistance
- response timing
- dynamic range
- signal processing
- integration
- coordination
- target cell response
what is the two classes of intracellular signalling that act like molecular switches
- GTPases
- kinases
what is a kinase
the addition of phosphate groups to hydroxyls on
- serine
- threonine
- tyrosine
the phosphate gets taken from ATP
what are GTPases
they are enzymes that hydrolyzes GTP to GDP changing the protein from active to inactive. Its role is to hydrolyze so the off position is preferable.
- it usually has help from some GTPase regulatory proteins like GAPs, RGSs, GDI & GEF
what are GAPs
they are GTPase activating protein
- changes GTP to GDP by increasing the hydrolyzing power of the GTPase thus shorten the protein mediated response
what are RGS
regulators of G protein signalling
- similar to GAP but done in a different location
- can deactivate a g protien
what are GDI
its a guanine nucleotide dissociation inhibitor
- keeps GDP bound so it can’t dissociate so protein remains in an inactive state
what are GEF
guanine nucleotide exchange factor
- factor needed to change from inactive to active by stimulating dissociation of GDP
What is a positive feedback?
when the protein activated by the stimulus is further activated by the protein it is signalling
eg. the Ca2+ activated Ca2+ channels open with calcium as its ligand
What is a negative feedback?
when the protein activated by the stimulus is inhibited by the protein it is signalling/ligand it is producing
eg. the IP3 channel gets inhibited when theres too much calcium and that means the Ca2+ channels will stop recievig ligands to open
How can cells change their sensitivity to signals (5 ways)
- receptor sequestration
- receptor down regulation
- receptor inactivation
- inactivation of signalling protein
- production of inhibitory protein
Explain receptor sequestration
controls the availably of the receptor by endocytosis, keeps it in and endosome and will return is when needed
Explain receptor down regulation
controls the availably of the receptor by endocytosis and degrades it by the lysosome
- slower in response because it will have to make the receptor again if needed
Explain receptor inactivation
the receptor is still at the plasma membrane but an inhibitor does allows the receptor to activate
- can be a phosphorylation or or dephosphorylated
Explain inactivation of signalling protein
the signalling protein downstream of the receptor gets inactivated by an inhibitor
Explain production of inhibitory protein
the receptor activates a signalling protein which then makes a inhibitory protein that stops the receptor
what are the different mechanisms by which intracellular signalling occurs
- preformed signalling complex on a scaffold protein
- assembly of signalling complex on an activated receptor
- assembly of a signalling complex on phosphoinositide docking sites
Briefly describe preformed signalling complex on a scaffold protein
a scaffold protein is attached to both the receptor and all he intracellular signalling proteins, when the receptor gets activated, the conformational change activates the intracellular signalling protein on the scaffold
- fast
Briefly describe assembly of a signalling complex an activated receptor
when the receptor gets activated, it gets phosphorylated by a kinase and that allows signalling proteins to bind
- bit slower than preformed
Briefly describe assembly of signalling complex on phosphoinositide docking sites
the activated receptors phosphorylate the PI docking sites which allows the signalling portioned to bind and get activated
what kind of molecules can bind to intracellular receptors
small hydrophobic ones but they need a carrier protein
- eg steroid and
that are the three classes of surface cell receptors?
- ion channel coupled receptors
- g-protein coupled receptors
- enzyme coupled receptors
