Signal Transduction Flashcards
Signal Transduction also known as
Cell signalling.
Cell to cell communication is essential for what?
Both multicellular and unicellular organisms.
Cells most often communicate with each other using what?
Chemical Signals
Example of Chemical Signals in use
Fight or Flight response triggered by epinephrine.
What did Earl W. Sutherland do?
He discovered that epinephrine causes the breakdown of glycogen, and so he suggested that cells receiving signals undergo three processes: reception, transduction, and response.
Reception
A signalling molecule (ligand) binds to a receptor protein, causing it to undergo a conformational change.
ligand
any chemical that binds to a receptor
The binding between a signalling molecule (ligand) and a receptor protein can be described as what?
Very specific and reversible.
Most signal receptors are
Plasma membrane proteins.
Most water-soluble signalling molecules do what?
Bind to specific sites on receptor proteins that span the plasma membrane.
How many types of membrane receptor proteins are there? What are they?
Three - G protein-coupled receptors, Receptor Tyrosine Kinases, and Ion Channel receptors (from information processing)
G protein coupled receptors name meaning
Called “G” because they require GTP
GTP
Guanosine Triphosphate
Receptor Tyrosine Kinase Function
Adds phosphate (hence Kinase) to amino acid tyrosine.
Largest family of cell-surface receptors
G protein-coupled receptors. (GPCRs)
Does the GPCR function alone? If not, with what does it function?
The GPCR is a plasma membrane receptor that functions with the help of a G protein.
G Protein function
The G protein acts as an on/off switch: when GDP (guanosine diphosphate) binds to the G protein, the G protein is inactive.
Steps of G-protein receptor function
Water-soluble signalling ligand binds to a G-protein receptor, resulting in a conformational change of the receptor. This conformational change allows the cytoplasmic side of the receptor to bind to an inactive G-protein, replacing its GDP with GTP, thereby activating it. The active G-protein binds to an enzyme in a transduction pathway, which causes it to once again become inactive.
Why are receptor tyrosine kinases (RTKs) so difficult to study?
A RTK can trigger multiple signal transduction pathways.
Abnormal functioning of RTKs is associated with what?
Cancer
Receptor Tyrosine Kinases Functioning Steps
Signalling molecule binds to receptor tyrosine kinase, which leads to dimerization. Dimerization causes the receptor to become phosphorylated and therefore active. The activated receptor binds to proteins in a transduction pathway.
Signalling molecules for Receptor Tyrosine Kinases (RTKs)
Growth Hormone.
Where are intracellular receptor proteins found?
Intracellular receptor proteins are found in the nucleus, or cytosol of target cells.
Intracellular
Inside of the cell
What kind of chemical messengers can bind to intracellular receptor proteins?
Small or hydrophobic chemical messengers.
Examples of chemical messengers that can readily pass through the membrane and bind to receptors
Steroids (hydrophobic) and thyroid hormones (small)
What does a chemical messenger, when binded to a intracellular receptor, form? What does this result do?
Chemical messengers bind to intracellular receptors to form an activated hormone-receptor complex. This can act as a transcription factor.
Transduction
Cascades of molecular interactions
Function of Cascades
Cascades relay signals from receptors to target molecules in the cell.
Cascades usually involve…
Many steps
Benefits of cascades
- Multiple steps allow for more opportunities of coordination and regulation of cellular response.
- Allows for amplification of signal.
The molecules that relay a signal from a receptor to a response are:
mainly proteins.
Cascade described with a colloquial term
Domino Effect.
2 pathways of transduction
- Protein phosphorylation and dephosphorylation
2. Second Messengers.
How is a signal transmitted?
A signal is transmitted by a series of protein phosphorylations.
Protein Kinases (function)
In phosphorylation and dephorylation system/cascade, the protein kinases transfer phosphates from ATP to serine or threonine.
What causes dephosphorylation?
Protein Phosphatases (PP) remove phosphates from proteins, a process called dephosphorylation.
The final protein in the cascade does what when activated?
Triggers a cellular response.
The phosphorylation and dephosphorylation system in the end does what?
It turns cellular activities on and off, or up or down (increasing or decreasing activity), as required.
Which protein kinases are activated? which are inactive?
Phosphorylated proteins are active, unphosphorylated proteins are inactive.
Second Messengers
Second Messengers are small, non-protein, water soluble molecules or ions.
How do second messengers spread throughout the cell?
By diffusion
Second messengers participate in which pathways?
Pathways initiated by GPCRs and RTKs.
Most common second messengers
Cyclic AMP, and (Calcium ions and inositol triphosphate (IP3))
two plasma membrane enzymes involved in cyclic AMP (cAMP)
Adenyl Cyclase and Phosphodiesterase
Adenyl Cyclase Function
Converts ATP to cAMP in response to an extracellular signal. Plasma membrane enzyme
Phosphodiesterase Function
Plasma membrane enzyme that converts cAMP to AMP to terminate the signal.
What triggers cAMP formation?
G proteins, G protein-coupled receptors, and protein kinases.
What does cAMP do?
cAMP usually activates protein kinase A
Some G protein systems can actually do what?
Some G protein systems can inhibit Adenyl Cyclase.
Why does calcium act as an important secondary messenger in many pathways?
Cells can easily regulate its concentration.
How do cells regulate the concentration of Calcium?
Using Ca2+ - ATPases, which pump calcium against the concentration gradient using ATP and gated calcium channels.
Signalling Molecule (ligand) alternative term
First messenger
Ca 2+, is it more concentrated inside or outside of the cell?
More concentrated outside of the cell
What helps regulate Ca2+ concentration?
inositol triphosphate (IP3)
How does inositol triphosphate regulate Ca2+ concentration in the cell? (Steps)
Phospholipase is activated by active G-protein. Active phosopholipase cleaves phosphotidylinositol into inositol triphosphate (IP3) and diacylglycerol. Inositol triphophate binds to Calcium gated channels in the endoplasmic reticulum (ER), opening them and causing an influx of Calcium ions into the cell, which activate the next protein in the cascade.
What does inositol triphosphate and diacylglycerol have in common?
They are both second messengers.
Cellular response takes place where?
in the cytoplasm or nucleus
Function of Cell signalling pathways
Cell signalling leads to regulation of transcription and cytoplasmic activities. Many signalling pathways regulate the synthesis of enzymes and other proteins, usually by turning genes on or off in the nucleus. The last activated molecule in a signalling pathway may function as a transcription factor. Some signalling pathways regulate the function of enzymes rather than their synthesis.
Example of a signalling pathway that regulates the function of an enzyme rather than its synthesis
Epinephrine
Relay molecules
Molecules that transmit the signal from the receptor to the cellular response.
Termination of the Signal Process
Decrease in ligand concentration causes more receptors to be unbound. Unbound receptors revert to an inactive state. Relay molecules return to an inactive state with the help of enzymes such as GTPases, phosphodiesterases, and protein phosphatases(PP)
GTPases
Hydrolyzes GTP attached to G-proteins
Phosphodiesterases
converts cAMP to AMP to terminate the signal
Protein Phosphatases (PP)
Deactivates active phosphorylated proteins by removing phosphates.