Concepts in cell signalling Flashcards
What does signalling allow cells to do?
Sense and respond to their environment
Communicate with each other
Extracellular signaling molecules
any molecule that can transmit signals between cells (ions, hormones, proteins, gases)
receptor
binds a signalling molecule
ligand
a signaling molecule that can be bound by a receptor
intracellular signaling molecule
any molecule that can transmit a signal within a cell (ions, metabolites, proteins)
includes secondary messengers
secondary messengers
non-protein small intracellular signalling molecules
effectors
receive signals to change cell behaviour
input/output
start or end of a pathway
upstream/downstream
relative positions in the pathway
how can extracellular signaling molecules act over short distances
contact-dependent, paracrine, autocrine
contact-dependent
two cells must be very close to connect membrane-bound signal in signaling cell to membrane-bound receptor in target cell
paracrine
signaling cell releases a local diffusible signal to target cell
autocrine
a cell secretes a diffusible signal for itself
what is signal movement restricted by
- internalization by cells
- degradation or destruction
- limited diffusion
- receptor expression
how can extracellular signaling molecules act over long distances
synaptic tranamission and endocrine
synaptic transmission
neuron extends an axon to reach (and make contact with) a distant target cell
endocrine cells
it secretes hormones into the bloodstream for long-range distribution in the body
how does receptor binding to ligands work
- receptors bind to specific molecules
- The target cell must express the receptor protein to receive the signal
- ligand binding activates the receptor
types of receptors
cell surface receptors and intracellular receptors
what rapid and reversible changes can be made to proteins during signaling
- different protein interactions
- increase/decrease enzyme activity
- changes in subcellular localization
- protein synthesis or degradation
how are changes to proteins during signaling achieved
phosphorylation
GTP-binding
ubiquitination
other small molecule binding
how are intracellular signals transmitted via protein phosphorylation
Protein kinase adds a phosphate group
Protein phosphatase removes a phosphate group
Phosphorylation can change protein structure or charge, this can affect protein activity, interactions or localization
It usually turns a protein or signalling pathway on BUT there are exceptions
GEFs
guanine nucleotide exchange factors
They help to exchange GDP for GTP
GAPs
GTPase activating enzymes
They help to activate the GTPase activity to hydrolyze GTP to GDP
What does GTP binding do?
It can affect protein activity, interactions or localization
it usually turns a protein/signalling pathway on
how can intracellular signaling be transmitted via protein ubiquitination
E1, E2, and E3 ligases help to activate the small protein ubiquitin and attach it to a target protein. Ubiquitin can change protein activity, localization or stability
what does monoubiqitylation signal for
histone regulation
what does multiuquitylation signal for
endocytosis
what does polyubiquitylation signal for
proteasomal degradation
DNA repair
How can intracellular signals be transmitted with small molecules
secondary messengers are small molecules (not proteins)
they are typically produced in large to amplify a signal
what are some examples of secondary molecules
Cyclic AMP
Ca2+
Diacylglycerol (DAG) lipid
Inositol triphosphate (IP3)
different speeds of signalling molecules
Synaptic transmission is very fast
Endocrine signalling is very slow since it requires blood circulation to distribute the signalling molecule
speeds of different intracellular pathways
- chnages to transcription and translation are slow
- changes to protein function are fast
- changes in membrane potential are extremely fast
- some signals can trigger both fast and slow responses
why are inhibitory steps important parts of signaling pathways
an inhibitor protein can inactivate a transcriptional regulator
Protein Kinase will phosphorylate the inhibitor protein inactivating it and deeming the transcriptional regulator active for gene expression
what do signalling pathways create
feedback
feedback creates a loop in the signaling pathway. without feedback the pathway would only be on when the signal is present
positive feedback
stimulus activates A
A activates B
B activates ore A (feedback)
output intensity is increased, output can continue even after the stimulus is removed
negative feedback
stimulus activates A
A activates B
B deactivates A (feedback)
2 patterns created by negative feednack
long delay and short delay
long delay
creates and oscillating output
short delay
output intensity is decreased (adaptation or densensitization)
dfferent mechanisma negative feedbakc can be achieved by
- negative feedback
- delayed feed forward
- receptor inactivation
- receptor sequestration
- receptor destruction
multiple signals required by cells
cell survival often requires specific signals
Additional signals can be required for growth, cell division and differentiation
can the same signals have different effects on different cells
yes
acetylocholine and heart pacemaker cells
decreased rate off iring
acetylcholine and salivary gland cell
secretion
receptor in heat pacemaker cell and salivary gland cells
same receptor but they have different downstream signals/effectors
acetylcholine and skeletal muscle cell
contraction
how can signals be specific in a complex cellular environment
- signaling complexes
- coincidence detectors
scaffold proteins
signaling complexes can be organized on scaffold proteins. they bind intracellular signaling proteins. they can limit protein movement and ensure signals are passed In order.
assemblies of scaffold proteins
- complex is assembles even in there is no signal
- some scaffolds only assemble once signal is activated
- phosphoinositide can help scaffold signaling proteins
how do some scaffolds assemble once a signaling is activated
- perception of the signal modifies the receptor (phosphorylation)
- intracellular signaling molecules bind to these modifications
- complex is assembles only when the signal is present
how do phosphoinositides help scaffold signaling proteins?
perception of the signal modified the membrane lipids (phosphorylation of phosphoinositide) Z
intracellular signaling molecules bind to new PIPs
protein interaction domains
SH3, SH2 and PTB, PH
they help signaling complexes assemble
SH3 domains
bind proline rich sequences
SH2 and PTB domains
they bind phophorylated tyrosines
PH domains
they bind phosphoinositides
Co-incidence detectors
They require multiple signals
Protein Y can be phosphorylated in two places
A or B alone can only trigger one phosphorylation site on Y
Y is only active if it has received both phosphorylation events
Y is a coincidence detector for pathways A and B
