Flashcards in Chapter 11 - Cell Communication Deck (61):
What can send, receive, interpret, and respond?
What is the signal transduction pathway?
Transduction sometimes occurs in a single step but more often requires a sequence of changes in a series of different molecules;
i.e. In mating of the yeast saccharomyces cerevisiae, there are two types of sexes, or mating types; a and α. Each type secretes a specific factor that binds to receptors only on the other type of the cell. When exposed to each other's mating factors, a pair of cells of opposite type change shape, grow toward each other, and fuse (mate). The new cell contains genes of both original cells. Once received by the yeast cell surface receptor, a mating signal is changed, or transduced, into a form that brings about the cellular response of mating. This occurs in a series of steps called the signal transduction pathway.
What is quorum sensing?
Bacterial cells secrete molecules that can be detected by other bacterial cells. Sensing the concentration of such signaling molecules allows bacteria to monitor the local density of cells. This quorum sensing allows bacterial populations to coordinate their behaviors in activities that require a given number of cells acting synchronously.
What are growth factors?
A class of local regulators in animal cells. Compounds that stimulate nearby target cells to grown and divide.
What are two ways in which animal cells may communicate with each other?
1. Local - direct contact; cell-cell recognition (synaptic), cell junctions; autocrine and paracrine
2. Long distance - endocrine signaling; i.e. hormones
What is paracrine signaling?
A type of local signaling in animals; numerous cells can simultaneously receive and respond to the molecules of growth factor produced by a single cell in their vicinity.
A secreting cell acts on nearby target cells by secreting molecules of a local regulator.
- Growth factors
- Synaptic (neurotransmitters; in the animal nervous system when a neurotransmitter is released in response to an electric signal
What is autocrine signaling?
The same cell secretes and responds; i.e. positive feedback - t cell activation by cytokines
What are hormones?
In multicellular organisms, one of many types of secreted chemicals that are formed in specialized cells, travel in body fluids, and act on specific target cells in other parts of the organism, changing the target cells' functioning.
Chemicals used for long distance signaling.
What is endocrine (hormonal) signaling?
Specialized cells release (secrete) hormone molecules, which travel via the circulatory system to other parts of the body, where they reach target cells that can recognize and respond to the hormones.
*The target cell response depends on the presence of specific receptors to that signal.
What are the two classes of release hormones?
1. Proteins - insulin (pancreas) and adrenaline (adrenal glands)
2. Steroids - estrogen
What are the three stages that cells receiving signals go through?
1. Reception - the target's cell detection of a signaling molecule coming from outside the cell; ligand / receptor (transmembrane or integral protein)
2. Transduction - converts the signal to a form that can bring about a specific cellular response; relay molecules
3. Response - the transduced signal finally triggers a specific cellular response. The response may be almost any imaginable cellular activity - such as catalysts by an enzyme, rearrangement of the cytoskeleton, protein activity, or activation of specific genes in the nucleus.
The signaling molecule is complementary in shape to a specific site on the receptor and attaches there, like a key in a lock. True or false?
What is a ligand?
A molecule that specifically binds to another molecule, often a larger one.
Ligand binding generally causes a receptor protein to undergo a change in shape. For many receptors, this shape change directly activates the receptor, enabling it to interact with other cellular molecules.
For some types of receptors, what is the immediate effect of ligand binding?
To cause the aggregation of two or more receptor molecule, which leads to further molecular events inside the cell. Most signal receptors are plasma membrane proteins, but others are located inside the cell.
What are the two types of ligands?
1. Agonist - mimics the action of a natural ligand; insulin, erythropoietin, L-dopa
2. Antagonist - competes with natural ligand for receptor; i.e. tamaxifin (binds to estrogen receptor)
What are the three main types of membrane receptors?
1. G protein-coupled receptors
2. Receptor tyrosine kinases
3. Ion channel receptors
Discuss G protein-coupled receptors (GPCRs).
G protein-coupled receptors are cell surface transmembrane receptors that work with the help of a G protein. G proteins bind to the energy rich GTP and are very similar in structure. Ligand binding activates the receptor, which then activates a specific G protein, which activates yet another protein, thus propagating the signal.
*GPCR systems are extremely widespread and diverse in their functions.
- Only found in eukaryotes
- Largest family of cell surface receptors (>1,000 known in humans)
- The target of 30%-50% of all modern medicinal drugs
- Ligands range from light-sensitive cmpds, odor, pheromones, hormones, and NTs
- Function; growth, pain, taste, immune system, vision, smell, etc...
- Structure - 7 transmembrane domains
*Activate a single transduction pathway.
Discuss receptor tyrosine kinases (RTKs).
Characterized by having enzymatic activity. A kinase is any enzyme that catalyzes the transfer of phosphate groups.
RTKs react to the binding of signaling molecules by forming dimers and then adding phosphate groups to tyrosines on the cytoplasmic part of the other monomer making up the dimer (two receptor monomers that associate closely with each other, forming a complex). Relay proteins in the cell can then be activated by binding to different phosphorylated tyrosines, allowing this receptor to trigger several pathways at once.
- Membrane receptors that attach phosphates to tyrosines
- *A receptor tyrosine kinase can trigger multiple signal transduction pathways at once
- Abnormal functioning of RTKs is associated with many types of cancers...
Discuss gated ion channels.
A type of membrane receptor containing a region that can act as a "gate" when the receptor changes shape. When a signaling molecule binds as a ligand to the receptor protein, the gate opens or closes, allowing or blocking the flow of specific ions. This regulates the flow of specific ions across the membrane. f
- Proteins that are selective for ions when they change shape
- Usually if a ligand binds to the receptor, the gate opens and specific ions can flow through the channel and rapidly change the concentration of that particular ion inside the cell
- When the ligand dissociates from the receptor, the gate closes and ions no longer enter the cell
What is an intracellular receptor?
Proteins that are found in either the cytoplasm or nucleus of target cells;
- Small or hydrophobic chemical messengers; i.e. steroid hormones and thyroid hormones of animals
- An activated hormone-receptor complex that can act as a transcription factor (TF), and is able to cause a response, like turning on specific genes
What are transcription factors?
Specialized proteins which control which genes are turned on - that is, which genes are transcribed into mRNA - in a particular cell at a particular time
What is transduction?
Cascades of molecular interactions relay signals from receptors to target molecules in the cell.
- Signal transduction usually involves multiple steps and can;
1. amplify a signal
2. provide more opportunities for coordination and regulation of the cellular response
Discuss signal transduction pathways.
- The binding of a signaling molecule to a receptor triggers the first step in a chain of molecular interactions
- Like falling dominoes; the receptor activates another protein, which activates another, and so on, until the protein producing the response is activated
- At each step, the signal is transduced into a different form, usually a shape change in a protein
What is a widespread cellular mechanism for regulating protein activity?
The phosphorylation and dephosphorylation of proteins
What is a protein kinase?
An enzyme that transfers phosphate groups from ATP to a protein
What two amino acids do most cytoplasmic protein kinases phosphorylate?
Serine and threonine; serine / threonine kinases are widely involved in signaling pathways in animals, plants, and fungi
*(tyrosine in RTKs)
What is a phosphorylation cascade?
A series of protein phosphorylations occurring sequentially in which each protein kinase phosphorylates the next, activating it; often found in signaling pathways
- A series of different proteins in a pathway are phosphorylated in turn, each protein adding a phosphate group to the next one in line
- Phosphorylation activates each protein, and dephosphorylation returns it to its inactive form
How does phosphorylation "make stuff happen"?
Activates, stimulates, excretes, moves, regulates, excites, produces, secretes, transports, and catalyzes
What are protein phosphatases?
Enzymes that can rapidly remove phosphate groups from proteins, a process called dephosphorylation; provide the mechanism for turning off the signal transduction pathway when the initial signal is no longer present. Phosphatases also make the protein kinases available for reuse, enabling the cell to respond again to an extracellular signal.
What is the "molecular switch"?
The phosphorylation-dephosphorylation system acts as a molecular switch in the cell, turning activities on or off, or up or down, as required.
What are second messengers?
Small, nonprotein, water soluble molecules or ions that spread throughout a cell by diffusion.
*Many signaling pathways involve second messengers; second messengers participate in pathways initiated by GPCRs and RTKs
What is cyclic AMP?
The most common second messenger; cyclic adenosine monophosphate (cAMP); the second messenger cAMP is made from ATP by an enzyme embedded in the plasma membrane, adenylyl cyclase, in response to a cellular signal - in this case, provided by epinephrine.
- Many signal molecules trigger formation of cAMP;
- G proteins, G protein-coupled receptors, and protein kinases
- cAMP usually activates protein kinase A, which phosphorylates various other proteins
- Further regulation of cell metabolism is provided by G-protein systems that inhibit adenylyl cyclase and inhibit phosphodiesterase...
Calcium ions (Ca2+) act as what?
A second messenger in many pathways;
- Ca2+ concentration in the cytosol is normally much lower than the concentration outside the cell
- A small change in number of calcium ions thus represents a relatively large percentage change in calcium concentration
What does cell signaling lead to?
Regulation of transcription or cytoplasmic activities.
The response may occur in the cytoplasm or the nucleus.
What do signaling pathways regulate?
- The synthesis of enzymes and other proteins
- Turning genes on or off in the nucleus
- The final activated molecule in the signaling pathway may function as a transcription factor
- Some of these pathways lead to cell division
What are four aspects of signal regulation to consider?
1. Signaling pathways generally AMPLIFY the cell's response to a single signaling event; the degree of amplification depends on the function of the specific molecules in the pathway
2. The many steps in a multistep pathway provide control points at which the cell's response can be further regulated, contributing to the SPECIFICITY of the response and allowing coordination with other signaling pathways
3. The overall EFFICIENCY of the response is enhanced by the presence of proteins known as scaffolding proteins
4. A crucial point in regulating the response is the TERMINATION of the signal
*A response to a signal may not be simply "on" or "off"
Discuss signal amplification.
- Elaborate enzyme cascades amplify the cell's response to a signal
- At each catalytic step in the cascade, the number of activated products can be much greater than in the proceeding step
- The amplification effect stems from the fact that these proteins persist in the active form long enough to process multiple molecules of substrate before they become inactive again
Discuss the specificity of cell signaling and coordination of the response.
- Different kinds of cells have different collections of proteins
- Different proteins allow cells to detect and respond to different signals
- The same signal can have different effects in cells with different proteins and pathways
- Pathway branching and "cross talk" further help the cell coordinate incoming signals
What are scaffolding proteins?
Large relay proteins to which several other relay proteins are simultaneously attached
Discuss "termination of the signal".
- Inactivation mechanisms are an essential aspect of cell signaling
- If ligand concentration falls, fewer receptors will be bound
- Unbound receptors revert to an inactive state
*For a cell of a multicellular organism to remain capable of responding to incoming signals, each molecular change in its signaling pathways must last only a short time... If a signaling pathway component becomes locked into one state, whether active or inactive, consequences for the organism can be dire... i.e. cholera*
What is apoptosis?
Controlled "cell suicide". Cells that are infected, are damaged, or have reached the end of their functional life span often undergo this "programmed cell death". During this process, cellular agents chop up the DNA and fragment the organelles and other cytoplasmic components. The cell shrinks and becomes lobed, and the cell's parts are packaged up in vesicles that are engulfed and digested by specialized scavenger cells, leaving no trace. Apoptosis protects neighboring cells from damage that they would otherwise suffer if a dying cell merely leaked out all its contents...
What are the two types of ligands?
What is the difference between agonist and antagonist drugs?
Agonist - mimics the action of the natural ligan; insulin, erythropoietin (a hormone secreted by the kidneys that increases the rate of production of red blood cells in response to falling levels of oxygen in the tissues), L-dopa (the precursor to the neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine)
Antagonist - competes with natural ligand for receptor; tamaxifin - binds to estrogen receptors (pharmaceutical), vectibix - an epidermal growth factor receptor (EGFR)
Categorize the chemical signals in terms of proximity of the communicating cells.
1. Local signaling - paracrine and synaptic; involves direct contact or the secretion of local regulators
2. Long distance signaling - endocrine (hormonal) signaling; animals also pass signals electrically
How do steroid hormones signal a cell?
Steroid hormones are intracellular receptors as they are small and hydrophobic and can therefore cross the hydrophobic interior of the membrane. Once the hormone has entered the cell, it may bind to an intracellular receptor in the cytoplasm or the nucleus.
What are the three secondary messengers and what triggers their release?
1. Cyclic AMP (cAMP) - the first messenger activates a G protein coupled receptor, which activates a specific G protein. In turn, the G protein activates adenylyl cyclase, which catalyzes the conversion of ATP to cAMP. The cAMP then acts as a second messenger and activates another protein, usually protein kinase A, leading to cellular responses.
2. Calcium ions - calcium ions flow out of the ER (down their concentration gradient), raising the CA2+ level in the cytosol; the process is initiated by the binding of a signaling molecule to a G protein-coupled receptor. A receptor tyrosine kinase could also initiate this pathway by activating phospholipase C.
*The CA2+ concentration in the cytosol is usually much lower than in the extracellular fluid and ER. Protein pumps in the plasma membrane and the ER membrane, driven by ATP, move CA2+ from the cytosol in the extracellular fluid and into the lumen of the ER. Mitochondrial pumps, driven by chemiosmosis, move CA2+ into mitochondria when the calcium level in the cytosol rises significantly.
3. Inositol triphosphate (IP3) - produced by cleavage of a certain kind of phospholipid in the plasma membrane. IP3 diffuses through the cytosol and binds to an IP3- gated calcium channel in the ER membrane, causing it to open. The process is initiated by the binding of a signaling molecule to a G protein-coupled receptor.
What are two possible outcomes for cell signaling?
1. Regulation of transcription
2. Cytoplasmic activities
What is reception?
A signaling molecule binds to a receptor protein, causing it to change shape
At each step in a signal transduction pathway, the signal is transduced into a different form, which commonly involves a shape change in a 1. ___ . Many signal transduction pathways include 2. ___ , in which a series of 3. ___ each add a phosphate group to the next one in line, activating it. Enzymes called 4. ___ remove the phosphate groups. The balance between 5. ___ and 6. ___ regulates the activity of proteins involved in the sequential steps of a 7. ___.
2. Phosphorylation cascades
3. Protein kinases
4. Protein phosphatases
7. Signal transduction pathway
1. ___ , such as the small molecule 2. ___ and the ion 3. ___ , diffuse readily through the cytosol and thus help broadcast signals quickly. Many 4. ___ activate 5. ___ , which makes cAMP from ATP. Cells use 6. ___ as a second messenger in both GPCR and RTK pathways. The tyrosine kinase pathways can also involve 7. ___ , which can trigger a subsequent increase in CA2+ levels.
1. Second messengers
2. Cyclic AMP
4. G proteins
5. Adenylyl cyclase
What is the final cellular response?
Gene expression / regulation
What does paracrine signaling involve?
Secreting cells acting on nearby target cells by discharging a local regulator into the extracellular fluid.
From the perspective of the cell receiving the message, the three stages of cell signaling are?
Signal reception, signal transduction, and cellular response
Phosphorylation cascades involving a series of protein kinases are useful for cellular signal transduction because they ___ .
Amplify the original signal many times
Which of the following would be inhibited by a drug that specifically blocks the addition of phosphate groups to proteins?
Receptor tyrosine kinase activity
Testosterone functions inside a cell by?
Binding with a receptor protein in the cytosol that enters the nucleus and activates genes
One of the major categories of receptors in the plasma membrane reacts by forming dimers, adding phosphate groups, then activating relay proteins. Which type does this?
Receptor tyrosine kinases
Hormones are chemical substances produces in one organ that are released into the bloodstream and affect the function of a target organ. For the target organ to respond to a particular hormone, it must ___ .
Have receptors that recognize and bind the hormone molecule
What is a type of local signaling in which a cell secretes a signal molecule that affects the same cell?
G-protein receptor with GTP bound to it is ___ .
In its active state