Module 9 (Cell Signaling) Flashcards
What is cell signaling?
Transferring information from the outside of the cell to obtain a response inside the cell (by sending and receiving chemical signals)
Elements for cell communication
- Signaling cell
- Signaling molecule
- Receptor molecule
- Receptor cell
Signaling in bacteria
A small peptide was discovered to be continuously synthesized by pneumococcal bacterial cells, cells have a receptor for this peptide on the surface, when it binds then the bacterium expresses genes that enable it to take up DNA from the environment
Receptor activation
Binding of signalling molecule
Signal transduction
The transmission of signal into the cell
Cellular response
It is specific for the target cell
Signal Termination
Stops the response of the target cell
Ligands
A specific molecule that is detected by receptors
- Sometimes crosses membrane to reach intracellular receptors
How is a receptor turned on?
Turned on when the signaling molecule binds to the receptor (activated)
What happens when a ligand binds to the ligand-binding site on its receptor?
A conformational change in the receptor triggers chemical reactions within the cytosol
What happens in signal transduction?
Message is transmitted to cell through the cytoplasm, which can stay in the cytoplasm or go to the nucleus, and then a series of proteins are activated/inactivated in a particular sequence
Once the signal has been received and acted upon, it is…
Terminated
Endocrine Signaling
Long distance communication where the signaling molecules travel through the bloodstream
- Uses hormones
Paracrine signaling
Short distance communication (approx 20 cells) where the signalling molecule travels via diffusion (usually small and water soluble)
Autocrine signaling
When a cell secretes a signaling molecule and is also the target cell (helpful for embryonic development)
Contact dependent signaling
A transmembrane protein on the surface of one cell acts as the signaling molecule, and a transmembrane protein on an adjacent cell acts as a receptor
Also known as juxtacrine signaling
Intracellular receptors
- Only works with nonpolar signaling molecules
- located in the cytoplasm or nucleus
Cell Surface Receptors
For polar signaling molecules
Contains three domains
- Extracellular domain
- Trans-membrane domain
- Cytoplasmic domain
GPCR
G protein-coupled receptors
- Associate with G proteins and bind GTP and GDP in the cytoplasm
Structure of G proteins
Alpha subunit
Beta subunit
Gamma subunit
What happens when GDP binds to the alpha subunit of G proteins?
The three subunits of G proteins are bound together. When it is bound to GTP, the protein is active.
What happens when a ligand binds to a GPCR
The binding activates a G protein by replacing GDP with GTP if the G protein is associated with the GPCR (active G protein)
When a G protein is active…
The alpha subunit dissociates and binds to a target protein to activate the target protein
How is heart rate influenced by GPCR systems?
When the G protein is active, it binds to adenylyl cyclase, which activates it and begins converting ATP into cyclic AMP. Cyclic AMP then activates Protein Kinase A, which phosphorylates proteins in heart muscle -> increases heart rate
What is cAMP known as?
- cyclic adenosine monophosphate
- A second messenger molecule
Protein Kinase A
Also known as PKA, and is an enzyme that phosphorylates proteins and increases the rate of contraction in the heart
Signal Amplification
A small amount of ligand can create a large reaction
- multiple G proteins are activated with one receptor
- each adenylyl cyclase produces large amounts of cAMP
- Each active PKA activates multiple protein targets
Binding Affinity
How tightly a receptor holds onto a ligand
When the ligand leaves the receptor…
No longer able to activate other proteins, signal terminates.
Phosphatases
Enzymes that dephosphorylate target proteins
Receptor Kinases
Becomes active when a ligand bonds, receptors associate into dimers, and they phosphorylate another protein on the inside of the cell.
Examples of receptor kinase signaling
Limb buds, Insulin signaling, wound healing
PDGF
Platelet-derived growth factor
- stimulates repair of tissues
- binds to receptor kinases
- released by platelets
MAP
Mitogen-Activated Protein
Ras
The signaling protein that is activated in the MAP kinase pathway
What happens when Ras is bound to GTP?
Triggers a kinase cascade
- At end of cascade, increased expression of cell division genes
Ligand-Gated Ion Channels
Respond to binding of a signalling molecule
Voltage-Gated Ion Channels
Respond to changes in voltage in the cell
Mechanically-gated Ion Channels
Respond to force applied to the cell