Hey girls, we had some random things to review in class today including signal transduction so hopefully this clears up any confusion in that area.
External signals are converted into responses within the cell
Evolution of Cell Signaling:
Signaling in microbes has much in common with processes in multicellular organisms, suggesting an early origin.
Local and Long–Distance Signaling:
In local signaling, animal cells may communicate by direct contact or by secreting local regulators, such as growth factors or neurotransmitters. For signaling over long distances, both animals and plants use hormones; animals also signal along nerve cells.
The Three Stages of Cell Signaling:
Earl Sutherland discovered how the hormone epinephrine acts on cells. The signal molecule epinephrine binds to receptors on a cell′s surface (reception), leading to a series of changes in the receptor and other molecules inside the cell (transduction) and finally to the activation of an enzyme that breaks down glycogen (response).
Reception: A signal molecule binds to a receptor protein, causing it to change shape
The binding between signal molecule (ligand) and receptor is highly specific. A conformational change in a receptor is often the initial transduction of the signal
Intracellular receptors are cytoplasmic or nuclear proteins. Signal molecules that are small or hydrophobic and can readily cross the plasma membrane use these receptors.
Receptors in the Plasma Membrane:
A G–protein–linked receptor is a membrane receptor that works with the help of a cytoplasmic G protein. Ligand binding activates the receptor, which then activates a specific G protein, which activates yet another protein, thus propagating the signal along a signal transduction pathway.
Receptor tyrosine kinases react to the binding of signal molecules by forming dimers and then adding phosphate groups to tyrosines on the cytoplasmic side of the other subunit of the receptor. Relay proteins in the cell can then be activated by binding to different phosphorylated tyrosines, allowing this receptor to trigger several pathways at once.
Specific signal molecules cause ligand–gated ion channels in a membrane to open or close, regulating the flow of specific ions.
Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell
Signal Transduction Pathways:
At each step in a pathway, the signal is transduced into a different form, commonly a conformational change in a protein.
Protein Phosphorylation and Dephosphorylation:
Many signal transduction pathways include phosphorylation cascades, in which a series of protein kinases each add a phosphate group to the next one in line, activating it. Phosphatase enzymes soon remove the phosphates.
Small Molecules and Ions as Second Messengers:
Second messengers, such as cyclic AMP (cAMP) and Ca2+, diffuse readily through the cytosol and thus help broadcast signals quickly. Many G proteins activate adenylyl cyclase, which makes cAMP from ATP. Cells use Ca2+ as a second messenger in both G–protein and tyrosine kinase pathways. The tyrosine kinase pathways can also involve two other second messengers, DAG and IP3. IP3 can trigger a subsequent increase in Ca2+ levels.
Response: Cell signaling leads to regulation of cytoplasmic activities or transcription
Cytoplasmic and Nuclear Responses:
In the cytoplasm, signaling pathways regulate, for example, enzyme activity and cytoskeleton rearrangement. Other pathways regulate genes by activating transcription factors, proteins that turn specific genes on or off.
Fine–Tuning of the Response:
Each catalytic protein in a signaling pathway amplifies the signal by activating multiple copies of the next component of the pathway; for long pathways, the total amplification may be a millionfold or more. The particular combination of proteins in a cell gives the cell great specificity in both the signals it detects and the responses it carries out. Scaffolding proteins can increase signal transduction efficiency. Pathway branching and cross–talk further help the cell coordinate incoming signals. Signal response is terminated quickly by the reversal of ligand binding.
1. Amplification of a chemical signal occurs when
a. a receptor in the plasma membrane activates several G– protein molecules while a signal molecule is bound to it.
b. a cAMP molecule activates one protein kinase molecule before being converted to AMP.
c. phosphorylase and phosphatase activities are balanced.
d. receptor tyrosine kinases dimerize upon ligand binding.
e. both a and d occur.
2. Which of the following provides the best evidence that cell–signaling pathways evolved early in the history of life?
a. They are seen in “primitive” cells such as yeast.
b. Yeast cells signal each other for mating.
c. Signal transduction molecules found in distantly related organisms are similar.
d. Signals can be sent long distances by cells.
e. Most signals are received by cell surface receptors.
3. Consider this pathway: epinephrine → G–protein–linked receptor → G protein → adenylyl cyclase → cAMP. Identify the second messenger.
b. G protein
d. adenylyl cyclase
e. G–protein–linked receptor
4. Which observation suggested to Sutherland the involvement of a second messenger in epinephrine′s effect on liver cells?
a. Enzymatic activity was proportional to the amount of calcium added to a cell–free extract.
b. Receptor studies indicated that epinephrine was a ligand.
c. Glycogen breakdown was observed only when epinephrine was administered to intact cells.
d. Glycogen breakdown was observed when epinephrine and glycogen phosphorylase were combined.
e. Epinephrine was known to have different effects on different types of cells.
5. Binding of a signal molecule to which type of receptor leads directly to a change in the distribution of anions and/or cations on opposite sides of the membrane?
a. receptor tyrosine kinase
b. G–protein–linked receptor
c. phosphorylated receptor tyrosine kinase dimer
d. ligand–gated ion channel
e. intracellular receptor
6. Protein phosphorylation is commonly involved with all of the following except
a. regulation of transcription by extracellular signal molecules.
b. enzyme activation.
c. activation of G–protein–linked receptors.
d. activation of receptor tyrosine kinases.
e. activation of protein kinase molecules.
7. Signal transduction pathways benefit cells for all of the following reasons except
a. they help cells respond to signal molecules that are too large or too polar to cross the plasma membrane.
b. they enable different cells to respond appropriately to the same signal.
c. they help cells use up phosphate generated by ATP breakdown.
d. they can amplify a signal.
e. variations in the signal transduction pathways can enhance response specificity.
8. Phosphorylation cascades involving a series of protein kinases are useful for cellular signal transduction because
a. they are species specific.
b. they always lead to the same cellular response.
c. they amplify the original signal manyfold.
d. they counter the harmful effects of phosphatases.
e. the number of molecules used is small and fixed.
9. The activation of receptor tyrosine kinases is always characterized by
a. dimerization and phosphorylation.
b. IP3 binding.
c. a phosphorylation cascade.
d. GTP hydrolysis.
e. channel protein conformational change.
10. Lipid–soluble signal molecules, such as testosterone, cross the membranes of all cells but affect only target cells because
a. only target cells retain the appropriate DNA segments.
b. intracellular receptors are present only in target cells.
c. most cells lack the Y chromosome required.
d. only target cells possess the cytosolic enzymes that transduce the testosterone.
e. only in target cells is testosterone able to initiate the phosphorylation cascade leading to activated transcription factor.