Lecture 8: Cell Signaling Flashcards
What are the three main steps of Cell Signaling?
Reception
Transduction
Response
Why do cells communicate?
Cells need to respond as a cell and as part of a whole tissue, reacting to signals from other cells and the environment, which can be chemical or other forms like light, taste, and smell.
What are the features of local signaling?
Local signaling involves signals acting on nearby target cells, such as paracrine signaling (e.g., growth factors like fibroblast growth factor) and synaptic signaling (e.g., neurotransmitters like acetylcholine).
What are examples of local signaling?
- growth factors such as fibroblast growth factor – FGF1 (paracrine)
- Neurotransmitters such as acetylcholine – ACh (synaptic)
- Can act on the signaling cell (autocrine)
What is long distance signaling?
Long-distance signaling occurs when hormones secreted from endocrine cells travel via the circulatory system to act on target cells, such as insulin secreted from pancreatic beta cells.
What are the 3 steps to cell signaling?
Reception
Transduction
Response
What are the names for the Signaling Molecule?
Ligand
First Messenger
Primary Messenger
What is Reception?
Signaling protein (otherwise called primary messenger or ligand) binds to a receptor protein causing a change in shape of the receptor protein
What is Transduction?
The altered receptor protein activates another protein (eg G-protein). The activated protein may cause a relay of changes causing other proteins to be activated.
Each activated protein causes a series of changes - often via phosphorylation.
What is Response?
All activated proteins cause a certain function or functions to occur in the cell
What is a TARGET receptor?
It’s the receptor with the complementary shape to the shape of the ligand - structure determines function
Is the type of cell receptors specific to the type of the cell?
No, there may be different receptor molecules on the cell surface membrane of one cell type at different points in time
What are the two types of receptors?
Intracellular and membrane-bound/cell surface receptors
What are intracellular receptors?
Primary messenger is generally hydrophobic and small - lipid soluble.
What are membrane bound / cell surface receptors?
Primary messenger is generally hydrophilic and/or large
examples include GPCR (G protein coupled receptor) and ligand-gated ion channels
What is a GPCR?
Transmembrane Proteins
Pass the Plasma Membrane seven times
Hundreds of different GPCRs exist
Many different ligands
G-protein coupled receptors are transmembrane proteins that pass through the membrane 7 times.
Its extracellular portion has ligand binding site and its inner portion has loops that interact with G proteins.
It is the target for 1/3 of all modern drugs
Where does specificity come from?
Specificity comes from the 3D molecular shape of the proteins involved, where only target receptors interact with specific signals (ligands) to activate signal transduction pathways.
Where are water-soluble molecule receptors found?
Receptors for water-soluble molecules are membrane-bound
What are examples of water-soluble molecule receptors?
G Protein Coupled Receptors, Receptor Tyrosine Kinases, and ligand-gated ion channels.
Why are water-soluble molecule receptors where they are?
Because the molecules cannot transverse the plasma membrane
Where are lipid-soluble molecule receptors found?
Receptors for lipid-soluble molecules are not membrane-bound and can be found in the cytoplasm or inside the nucleus
What are examples of lipid-soluble molecule receptors?
Receptors for hormones like testosterone and estrogen.
What are G-protein coupled receptors (GPCRs)?
GPCRs are transmembrane proteins that pass through the plasma membrane seven times, with hundreds of different GPCRs existing for diverse functions, including development and sensory reception.
What are G Proteins?
G proteins are molecular switches which are usually inactive when GDP is bound and then become switched on or active when bound to GTP (guanosine triphosphate)
What do G Proteins use as energy?
GDP, or GTP
Guanosine Triphosphate (Similar to ATP)
What is the first phase of GPCR coupling?
At rest, receptor is unbound and G protein is bound to GDP (inactive). The enzyme in the plasma membrane is in an inactive state.
What is the second phase of GPCR coupling?
Ligand binds receptor, and binds the G Protein.
The receptor and G Protein changes shape.
GTP displaces GDP
The enzyme is inactive
When the ligand binds to the receptor site of the protein, the receptor changes shape allowing G protein with GTP (hence active) to bind to the receptor molecule. The enzyme is still inactive at this stage.
What is the third phase of GPCR coupling?
Activated G Protein dissociates from receptor.
Enzyme is activated to elicit a cellular response.
The enzyme and G Protein changes shape.
Activated G protein dissociates from receptor along with attached GTP. Enzyme is activated by the G protein to elicit a cellular response.
What is the fourth phase of GPCR coupling?
G protein has GTPase activity (GTP is broken down into GDP and P) causing its release from the enzyme reverting back to resting state.
What are Ligand Gated Ion Channels?
A ligand controlled gate that allows Ions through their channel.
A receptor protein containing a gate. Binding of ligands to the receptor causes change in shape opening the gate and allowing entry of ions.
Ligand-gated ion channels are channel receptors that contain a “gate” which opens or closes as the receptor changes shape upon ligand binding, allowing specific ions to flow into the cell.
What is an ion channel?
An ion channel is a membrane protein that allows specific ions to travel through it, and an ion channel receptor responds to ligand binding to facilitate this process.
What is a receptor in the context of cell signaling?
A receptor is a molecule or protein that responds to a specific ligand, initiating a cellular response.
What is a ligand?
A ligand is a signaling molecule that binds specifically to another protein, such as a receptor.
What is the first phase of a Ligand Gated Ion Channel?
What is the second phase of a Ligand Gated Ion Channel?
What is the third phase of a Ligand Gated Ion Channel?
Which body system relies heavily on Ligand Gated Ion Channels?
The nervous system.
Released neurotransmitters bind as ligands to ion channels on target cells to propagate action potentials.
What is step two of Cell Signaling?
Signal Transduction
What is step one of Cell Signaling?
What is step three of Cell Signaling?
What are Protein Kinases?
Enzymes that transfer a phosphate group from ATP to another (specific) protein (Kinases Phosphorylate).
Typically, this activates the protein.
What are examples of Second Messengers?
cAMP (Cyclic AMP)
Ca²⁺ (Calcium)
IP₃ (Inositol Trisphosphate)
What are some features of Second Messengers?
Always small
Never proteins
Where does calcium pumps pump into?
Out of Cell
Into ER
Into Mitochondria
Why are there so many steps to Cell Signaling?
Allows for specificity of response (Temporal, Spatial) despite molecules in common.
Multiple steps amplify the response, provide control points, allow for specificity of response, and enable coordination with other signaling pathways.
What is cAMP broken down by?
Phosphodiesterase (PDE)
