9.3: Response to the Cellular Signal - Biology

9.3: Response to the Cellular Signal - Biology

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9.3: Response to the Cellular Signal

9.3: Response to the Cellular Signal - Biology

Tutorial to help you answer the question

A protein receptor binds a hormone outside the cell membrane and activates a protein kinase inside the cell. Is the receptor a peripheral or integral membrane protein?


Membrane receptors are peripheral, or associated with the surface of the bilayer. Association with a hormone results in the release of a lipid signal that activates protein kinases.


Membrane receptors associated with signaling are all integral membrane proteins that can transmit signals through the lipid bilayer.

Chemical signaling

There are two kinds of communication in the world of living cells. Communication between cells is called intercellular signaling, and communication within a cell is called intracellular signaling. An easy way to remember the distinction is by understanding the Latin origin of the prefixes: inter- means &ldquobetween&rdquo (for example, intersecting lines are those that cross each other) and intra- means &ldquoinside&rdquo (like intravenous).

Chemical signals are released by signaling cells in the form of small, usually volatile or soluble molecules called ligands. A ligand is a molecule that binds another specific molecule, in some cases, delivering a signal in the process. Ligands can thus be thought of as signaling molecules. Ligands interact with proteins in target cells, which are cells that are affected by chemical signals these proteins are also called receptors. Ligands and receptors exist in several varieties however, a specific ligand will have a specific receptor that typically binds only that ligand.

Forms of Signaling

There are four categories of chemical signaling found in multicellular organisms: paracrine signaling, endocrine signaling, autocrine signaling, and direct signaling across gap junctions (Figure 9.2). The main difference between the different categories of signaling is the distance that the signal travels through the organism to reach the target cell. Not all cells are affected by the same signals.

Figure 9.2. Forms of chemical signaling: autocrine, gap junctions, paracrine, and endocrine.

In chemical signaling, a cell may target itself (autocrine signaling), a cell connected by gap junctions, a nearby cell (paracrine signaling), or a distant cell (endocrine signaling). Paracrine signaling acts on nearby cells, endocrine signaling uses the circulatory system to transport ligands, and autocrine signaling acts on the signaling cell. Signaling via gap junctions involves signaling molecules moving directly between adjacent cells.

Paracrine signaling

Signals that act locally between cells that are close together are called paracrine signals. Paracrine signals move by diffusion through the extracellular matrix. These types of signals usually elicit quick responses that last only a short amount of time. In order to keep the response localized, paracrine ligand molecules are normally quickly degraded by enzymes or removed by neighboring cells. Removing the signals will reestablish the concentration gradient for the signal, allowing them to quickly diffuse through the intracellular space if released again.

One example of paracrine signaling is the transfer of signals across synapses between nerve cells. A nerve cell consists of a cell body, several short, branched extensions called dendrites that receive stimuli, and a long extension called an axon, which transmits signals to other nerve cells or muscle cells. The junction between nerve cells where signal transmission occurs is called a synapse. A synaptic signal is a chemical signal that travels between nerve cells. Signals within the nerve cells are propagated by fast-moving electrical impulses. When these impulses reach the end of the axon, the signal continues on to a dendrite of the next cell by the release of chemical ligands called neurotransmitters by the presynaptic cell (the cell emitting the signal). The neurotransmitters are transported across the very small distances between nerve cells, which are called chemical synapses (Figure 9.3). The small distance between nerve cells allows the signal to travel quickly this enables an immediate response, such as, Take your hand off the stove!

When the neurotransmitter binds the receptor on the surface of the postsynaptic cell, the electrochemical potential of the target cell changes, and the next electrical impulse is launched. The neurotransmitters that are released into the chemical synapse are degraded quickly or get reabsorbed by the presynaptic cell so that the recipient nerve cell can recover quickly and be prepared to respond rapidly to the next synaptic signal.

Figure 9.3. Synapse showing neurotransmitter release.

The distance between the presynaptic cell and the postsynaptic cell&mdashcalled the synaptic gap&mdashis very small and allows for rapid diffusion of the neurotransmitter. Enzymes in the synapatic cleft degrade some types of neurotransmitters to terminate the signal.

Endocrine signaling

Signals from distant cells are called endocrine signals, and they originate from endocrine cells. (In the body, many endocrine cells are located in endocrine glands, such as the thyroid gland, the hypothalamus, and the pituitary gland.) These types of signals usually produce a slower response but have a longer-lasting effect. The ligands released in endocrine signaling are called hormones, signaling molecules that are produced in one part of the body but affect other body regions some distance away.

Hormones travel the large distances between endocrine cells and their target cells via the bloodstream, which is a relatively slow way to move throughout the body. Because of their form of transport, hormones get diluted and are present in low concentrations when they act on their target cells. This is different from paracrine signaling, in which local concentrations of ligands can be very high.

Autocrine signaling

Autocrine signals are produced by signaling cells that can also bind to the ligand that is released. This means the signaling cell and the target cell can be the same or a similar cell (the prefix auto- means self, a reminder that the signaling cell sends a signal to itself). This type of signaling often occurs during the early development of an organism to ensure that cells develop into the correct tissues and take on the proper function. Autocrine signaling also regulates pain sensation and inflammatory responses. Further, if a cell is infected with a virus, the cell can signal itself to undergo programmed cell death, killing the virus in the process. In some cases, neighboring cells of the same type are also influenced by the released ligand. In embryological development, this process of stimulating a group of neighboring cells may help to direct the differentiation of identical cells into the same cell type, thus ensuring the proper developmental outcome.

Direct signaling across gap junctions

Gap junctions in animals and plasmodesmata in plants are connections between the plasma membranes of neighboring cells. These water-filled channels allow small signaling molecules, called intracellular mediators, to diffuse between the two cells. Small molecules, such as calcium ions (Ca2+), are able to move between cells, but large molecules like proteins and DNA cannot fit through the channels. The specificity of the channels ensures that the cells remain independent but can quickly and easily transmit signals. The transfer of signaling molecules communicates the current state of the cell that is directly next to the target cell this allows a group of cells to coordinate their response to a signal that only one of them may have received. In plants, plasmodesmata are ubiquitous, making the entire plant into a giant, communication network.

Types of Receptors

Receptors are protein molecules in the target cell or on its surface that bind ligand. There are two types of receptors, internal receptors and cell-surface receptors.

Internal receptors

Internal receptors, also known as intracellular or cytoplasmic receptors, are found in the cytoplasm of the cell and respond to hydrophobic ligand molecules that are able to travel across the plasma membrane. Once inside the cell, many of these molecules bind to proteins that act as regulators of mRNA synthesis (transcription) to mediate gene expression. Gene expression is the cellular process of transforming the information in a cell&rsquos DNA into a sequence of amino acids, which ultimately forms a protein. When the ligand binds to the internal receptor, a conformational change is triggered that exposes a DNA-binding site on the protein. The ligand-receptor complex moves into the nucleus, then binds to specific regulatory regions of the chromosomal DNA and promotes the initiation of transcription (Figure 9.4). Transcription is the process of copying the information in a cells DNA into a special form of RNA called messenger RNA (mRNA) the cell uses information in the mRNA (which moves out into the cytoplasm and associates with ribosomes) to link specific amino acids in the correct order, producing a protein. Internal receptors can directly influence gene expression without having to pass the signal on to other receptors or messengers.

Figure 9.4. Hydrophobic signaling.

Hydrophobic signaling molecules typically diffuse across the plasma membrane and interact with intracellular receptors in the cytoplasm. Many intracellular receptors are transcription factors that interact with DNA in the nucleus and regulate gene expression.

Cell-surface receptors

Cell-surface receptors, also known as transmembrane receptors, are cell surface, membrane-anchored (integral) proteins that bind to external ligand molecules. This type of receptor spans the plasma membrane and performs signal transduction, in which an extracellular signal is converted into an intercellular signal. Ligands that interact with cell-surface receptors do not have to enter the cell that they affect. Cell-surface receptors are also called cell-specific proteins or markers because they are specific to individual cell types.

Because cell-surface receptor proteins are fundamental to normal cell functioning, it should come as no surprise that a malfunction in any one of these proteins could have severe consequences. Errors in the protein structures of certain receptor molecules have been shown to play a role in hypertension (high blood pressure), asthma, heart disease, and cancer.

Each cell-surface receptor has three main components: an external ligand-binding domain, a hydrophobic membrane-spanning region, and an intracellular domain inside the cell. The ligand-binding domain is also called the extracellular domain. The size and extent of each of these domains vary widely, depending on the type of receptor. Cell-surface receptors are involved in most of the signaling in multicellular organisms. There are three general categories of cell-surface receptors: ion channel-linked receptors, G-protein-linked receptors, and enzyme-linked receptors.

Ion channel-linked receptors bind a ligand and open a channel through the membrane that allows specific ions to pass through. To form a channel, this type of cell-surface receptor has an extensive membrane-spanning region. In order to interact with the phospholipid fatty acid tails that form the center of the plasma membrane, many of the amino acids in the membrane-spanning region are hydrophobic in nature. Conversely, the amino acids that line the inside of the channel are hydrophilic to allow for the passage of water or ions. When a ligand binds to the extracellular region of the channel, there is a conformational change in the proteins structure that allows ions such as sodium, calcium, magnesium, and hydrogen to pass through (Figure 9.5)

Figure 9.5. A closed gated ion channel. Gated ion channels form a pore through the plasma membrane that opens when the signaling molecule binds. The open pore then allows ions to flow into or out of the cell.

G-protein-linked receptors bind a ligand and activate a membrane protein called a G-protein. The activated G-protein then interacts with either an ion channel or an enzyme in the membrane (Figure 9.6). All G-protein-linked receptors have seven transmembrane domains, but each receptor has its own specific extracellular domain and G-protein-binding site.

Cell signaling using G-protein-linked receptors occurs as a cyclic series of events. Before the ligand binds, the inactive G-protein can bind to a newly revealed site on the receptor specific for its binding. Once the G-protein binds to the receptor, the resultant shape change activates the G-protein, which releases GDP and picks up GTP. The subunits of the G-protein then split into the &alpha subunit and the &beta&gamma subunit. One or both of these G-protein fragments may be able to activate other proteins as a result. After awhile, the GTP on the active &alpha subunit of the G-protein is hydrolyzed to GDP and the &beta&gamma subunit is deactivated. The subunits reassociate to form the inactive G-protein and the cycle begins anew.

Figure 9.6. Heterotrimeric G proteins have three subunits: &alpha, &beta, and &gamma. When a signaling molecule binds to a G-protein-coupled receptor in the plasma membrane, a GDP molecule associated with the &alpha subunit is exchanged for GTP. The &beta and &gamma subunits dissociate from the &alpha subunit, and a cellular response is triggered either by the &alpha subunit or the dissociated &beta&gamma pair. Hydrolysis of GTP to GDP terminates the signal.

G-protein-linked receptors have been extensively studied and much has been learned about their roles in maintaining health. Bacteria that are pathogenic to humans can release poisons that interrupt specific G-protein-linked receptor function, leading to illnesses such as pertussis, botulism, and cholera. In cholera (Figure 9.7), for example, the water-borne bacterium Vibrio cholerae produces a toxin, choleragen, that binds to cells lining the small intestine. The toxin then enters these intestinal cells, where it modifies a G-protein that controls the opening of a chloride channel and causes it to remain continuously active, resulting in large losses of fluids from the body and potentially fatal dehydration as a result.

Figure 9.7. Transmitted primarily through contaminated drinking water, cholera is a major cause of death in the developing world and in areas where natural disasters interrupt the availability of clean water. The cholera bacterium, Vibrio cholerae, creates a toxin that modifies G-protein-mediated cell signaling pathways in the intestines. Modern sanitation eliminates the threat of cholera outbreaks, such as the one that swept through New York City in 1866. This poster from that era shows how, at that time, the way that the disease was transmitted was not understood. (credit: New York City Sanitary Commission)

Enzyme-linked receptors are cell-surface receptors with intracellular domains that are associated with an enzyme. In some cases, the intracellular domain of the receptor itself is an enzyme. Other enzyme-linked receptors have a small intracellular domain that interacts directly with an enzyme. The enzyme-linked receptors normally have large extracellular and intracellular domains, but the membrane-spanning region consists of a single alpha-helical region of the peptide strand. When a ligand binds to the extracellular domain, a signal is transferred through the membrane, activating the enzyme. Activation of the enzyme sets off a chain of events within the cell that eventually leads to a response. One example of this type of enzyme-linked receptor is the tyrosine kinase receptor (Figure 9.8). A kinase is an enzyme that transfers phosphate groups from ATP to another protein. The tyrosine kinase receptor transfers phosphate groups to tyrosine molecules (tyrosine residues). First, signaling molecules bind to the extracellular domain of two nearby tyrosine kinase receptors. The two neighboring receptors then bond together, or dimerize. Phosphates are then added to tyrosine residues on the intracellular domain of the receptors (phosphorylation). The phosphorylated residues can then transmit the signal to the next messenger within the cytoplasm.

Figure 9.8. A receptor tyrosine kinase is an enzyme-linked receptor with a single transmembrane region, and extracellular and intracellular domains. Binding of a signaling molecule to the extracellular domain causes the receptor to dimerize. Tyrosine residues on the intracellular domain are then autophosphorylated, triggering a downstream cellular response. The signal is terminated by a phosphatase that removes the phosphates from the phosphotyrosine residues.

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T cells have emerged as a powerful tool in the treatment of cancer, allowing for high specificity, extended efficacy, and reduced off-target effects. Adoptive T cell therapy has shown particular promise in the treatment of blood cancers [1,2]. However, a current barrier to wide use of this approach is the reliable production of T cells that comprise the therapeutic agent. In particular, this production involves the ex vivo expansion of a small, starting population of cells derived from the individual undergoing treatment [3,4]. Expansion can be initiated by activating T cells using a synthetic system, most commonly polystyrene beads that present antibodies to the CD3 and CD28 receptors on the T cell surface this commercial Dynabeads system provides signaling normally associated with Antigen Presenting Cells (APCs) in a manufactured format [5]. While successful, this system faces difficulty in activating T cells isolated from patients undergoing cancer treatment, in which T cells exhibit an exhausted phenotype [6].

One approach towards improving T cell expansion arose from the discovery that T cells can sense the mechanical properties of an activating substrate. Oɼonnor et al. demonstrated that mixed CD4+/CD8+ populations of primary human T cells activated on flat polydimethylsiloxane (PDMS) elastomer surfaces presenting anti-CD3 and anti-CD28 antibodies exhibit greater expansion on soft (Young's modulus E

100 kPa) compared to stiff (E

2 MPa) surfaces. The use of soft PDMS to enhance T cell expansion was confirmed in other formats such as beads and scaffolds, demonstrating new capabilities for cell production, including rescue of expansion for exhausted T cells [7,8]. However, key aspects of this mechanosensing behavior are not well understood. In particular, an opposite trend of activation was seen for mouse CD4 + T cells responding to polyacrylamide (PA) gels ranging from 10 to 200 kPa in Young's Modulus, with higher activation observed on higher stiffness [9]. Moreover, the ranges of elastic moduli of the PDMS materials used in previous reports are much higher than that associated with physiological tissues (few to hundreds of kPa). A later report by Saitakis et al. confirmed that T cells respond to substrate stiffness in this nominally superphysiological range, but also showed increased short-term function (migration and cytokine secretion) of human T cells with increasing stiffness [10]. Together, these studies suggest that T cell mechanosensing may be biphasic, exhibiting a peak between a range of substrate elastic moduli the existence of and range for this peak may be dependent on the specific type of substrate and activating ligands that are presented to T cells. This concept is supported by a later study by Wahl et al. that demonstrated biphasic spreading as a function of substrate stiffness [11]. However, that study was limited to early cell responses and focused predominantly on the Jurkat cell line, which exhibits multiple signaling defects in comparison to normal human T cells [12]. These studies also did not link early T cell responses and subsequent functionality of activated T cells.

Towards an improved understanding of T cell mechanosensing, this report examines the response of human CD4 + /CD8 + T cells activated on PA gels, controlling both substrate stiffness and density of activating ligands. Our results demonstrate a biphasic response of T cell expansion with respect to these parameters. Notably, short-term T cell responses showed limited correlation with expansion. We explore the transcriptome of mechanosensitive T cell activation to determine how stiffness induces different activation programs that regulates observed functional differences.

How does caffeine affect the body?

Caffeine--the drug that gives coffee and cola its kick--has a number of physiological effects. At the cellular level, caffeine blocks the action of a chemical called phosphodiesterase (PDE). Inside cells, PDE normally breaks down the second chemical messenger cyclic adenosine monophosphate (cAMP). Many hormones and neurotransmitters cannot cross the cell membrane, and so they exert their actions indirectly via such second messengers when they bind to a receptor on the surface of a cell, it initiates a chemical chain reaction called an enzyme cascade that results in the formation of second messenger chemicals.

Historically, cAMP was the first second messenger ever described. Now, however, scientists have identified several major classes of second messengers, which are generally formed in similar ways through a set of molecules called G proteins. The advantage of such a complex system is that an extracellular signal can be greatly amplified in the process, and so have a massive intracellular effect.

Thus, when caffeine stops the breakdown of cAMP, its effects are prolonged, and the response throughout the body is effectively amplified. In the heart, this response prompts norepinephrine--also called noradrenalin--and a related neurotransmitter, epinephrine, to increase the rate and force of the muscle's contractions. Although the two act in concert, norepinephrine is released by sympathetic nerves near the pacemaker tissue of the heart, whereas epinephrine is released primarily by the adrenal glands. These chemical messages lead to "fight or flight" behavior. During stressful or emergency conditions, they raise the rate and force of the heart, thereby increasing the blood pressure and delivering more oxygen to the brain and other tissues.

Caffeine would be expected to have this effect on any animals that used these neurotransmitters to regulate their heartbeat. Generally speaking, the effects of caffeine are most pronounced in birds and mammals. Reptiles have some response, and lower vertebrates and invertebrates have rather small or no responses. From an evolutionary perspective, fish and amphibians don't show as strong a response to epinephrine and norepinephrine as the higher vertebrates, and they lack a well-developed sympathetic (that is, stimulatory) enervation to heart.

Chronic Lymphocytic Leukemia

Farrukh T. Awan , John C. Byrd , in Hematology (Seventh Edition) , 2018

CD38 Expression

Retrospective studies have shown that CD38 is an independent prognostic marker in CLL, demonstrating that high CD38 expression is associated with both a shorter time from diagnosis to treatment and inferior survival. CD38 functional studies using CD31 and plexin B1 transfected fibroblasts have provided a biologic explanation for this observation. CD38 interaction with its ligand, CD31, in the presence of IL-2 results in upregulation of the survival receptor CD100 exclusively on proliferating CLL cells. This occurs with concomitant downmodulation of CD72, a negative regulator of immune response. The interaction between CD38 and CD100 on CLL cells and CD31 and plexin B1, respectively, on transfected fibroblasts results in enhanced survival and growth of CLL cells. Furthermore, the presence of nurse-like cells in CLL patients expressing high levels of CD31 and plexin B1 corroborates the interplay of CD38 and CD31 and provides further evidence of activation of circulating CD38-positive CLL cells by the microenvironment. This finding provides an explanation for the aggressive nature of these CLL clones.

Why are cancer researchers excited about biological pathways?

Until recently, many researchers hoped that most forms of cancer were driven by single genetic mutations and could be treated by drugs that target those specific mutations. Much of that hope was based on the success of imatinib (Gleevec), a drug that was specifically designed to treat a blood cancer called chronic myeloid leukemia (CML). CML occurs because of a single genetic glitch that leads to the production of a defective protein that spurs uncontrolled cell growth. Gleevec binds to that protein, stopping its activity and producing dramatic results in many CML patients.

Unfortunately, the one-target, one-drug approach has not held up for most other types of cancer. Recent projects that deciphered the genomes of cancer cells have found an array of different genetic mutations that can lead to the same cancer in different patients.

Thus, instead of attempting to discover ways to attack one well-defined genetic enemy, researchers now face the prospect of fighting many enemies.

Fortunately, this complex view can be simplified by looking at which biological pathways are disrupted by the genetic mutations. With further research on biological pathways and the genetic profiles of particular tumors, drug developers might be able to focus their attention on just two or three pathways. Patients could then receive the one or two drugs most likely to repair the pathways affected in their particular tumors.

Until recently, many researchers hoped that most forms of cancer were driven by single genetic mutations and could be treated by drugs that target those specific mutations. Much of that hope was based on the success of imatinib (Gleevec), a drug that was specifically designed to treat a blood cancer called chronic myeloid leukemia (CML). CML occurs because of a single genetic glitch that leads to the production of a defective protein that spurs uncontrolled cell growth. Gleevec binds to that protein, stopping its activity and producing dramatic results in many CML patients.

Unfortunately, the one-target, one-drug approach has not held up for most other types of cancer. Recent projects that deciphered the genomes of cancer cells have found an array of different genetic mutations that can lead to the same cancer in different patients.

Thus, instead of attempting to discover ways to attack one well-defined genetic enemy, researchers now face the prospect of fighting many enemies.

Fortunately, this complex view can be simplified by looking at which biological pathways are disrupted by the genetic mutations. With further research on biological pathways and the genetic profiles of particular tumors, drug developers might be able to focus their attention on just two or three pathways. Patients could then receive the one or two drugs most likely to repair the pathways affected in their particular tumors.

Sensing of self nucleic acids can result in autoimmunity

Although all the defense mechanisms described above are designed for the recognition of microbial nucleic acids, they can in some circumstances lead to the recognition of host DNA and RNA and the development of autoimmunity [47]. TLRs specific for nucleic acids are normally localized to the endosomal compartment, which may be the safeguard against contact with self DNA [5]. Unfortunately for the host, endogenous RNA and DNA are also able to activate TLR7 and TLR9 if they enter the endosomal compartment. A rich potential source of self RNA and DNA are the remains of host cells that have died via necrosis or apoptosis. Normally such apoptotic debris appears to be cleared rapidly by macrophages, which in humans do not express TLR7 or TLR9. But if there is a delay in apoptotic clearance, or if there are autoantibodies that interact with the antigens exposed on the apoptotic cells, this material can be misdirected to pDCs and B cells, where the nucleic acids can activate TLR7 and/or TLR9, resulting in the secretion of type I interferons by pDCs and the differentiation of B cells into plasma cells. Such a mechanism is likely to be the cause of pDC secretion of type I interferons in systemic lupus erythematosus (SLE) patients, in which increased serum concentrations of interferon-α correlate with disease activity and probably contribute to disease pathogenesis. In the mouse model of SLE, the genetic locus Y chromosome-linked autoimmune accelerator (Yaa) acts as a disease accelerator, promoting SLE in genetically susceptible mouse strains. Recent genetic studies revealed that Yaa is a duplication and translocation of the TLR7 gene from the X chromosome onto the Y chromosome, increasing the dosage of the TLR7 gene in the cell [48, 49]. Further studies showed that the gene dosage of TLR7 is directly related to the risk of autoimmunity [50].

TLR-independent mechanisms for the recognition of self nucleic acids also contribute to autoimmunity. Deoxyribo-nuclease II (DNase II) in macrophages cleaves the DNA of engulfed apoptotic cells and of engulfed nuclei that have been expelled from erythroid precursor cells. In mice deficient in DNase II, genomic DNA cannot be degraded and accumulates in the macrophage phagosome, leading to TLR-independent, interferon-mediated autoimmune pathology [51]. Whether DAI or other cytosolic DNA sensors contribute to such autoimmunity awaits further investigation.

The discovery of pattern recognition receptors has thus revolutionized our understanding of innate immunity, explaining why and how multiple and diverse infectious agents are recognized by a limited number of innate immune receptors that trigger antimicrobial responses [1]. We are beginning to appreciate how a variety of such receptors at distinct cellular localizations recognize non-self nucleic acids derived from infectious microorganisms and initiate a proper immune response against them, while at the same time maintaining tolerance to self DNA and RNA to prevent development of autoimmunity. How such a delicate balance is established is not well understood and it probably involves both the receptors themselves and the way host nucleic acids are handled in the cell. For example, sequestration of certain TLRs in the endosomal compartments and packaging of mammalian DNA into high-order chromatin structure may both prevent the accidental activation of innate responses to self nucleic acids. It will also be important to dissect the molecular mechanisms and structural basis of the interactions of these receptors with their ligands, a task that should become easier following the recent elucidation of the structures of several TLRs [52–55]. Finally, the mechanisms underlying the sensing of cytosolic DNA by DAI and other possible factors have not yet been established and await further investigation. Eventually, research on innate recognition of non-self nucleic acids is likely to be translated into the development of new strategies for the prevention and therapy of infectious and autoimmune diseases.

9.3: Response to the Cellular Signal - Biology

Living organisms constantly receive and interpret signals from their environment. Signals can come in the form of light, heat, water, odors, touch, or sound. Cells of multi-cellular organisms also receive signals from other cells, including signals for cell division and differentiation. The majority of cells in our bodies must constantly receive signals that keep them alive and functioning. All organisms also have signaling systems that warn of the presence of pathogens, leading to a protective response.

The key concept is that the many signaling systems of biology have very similar or related steps. The same signaling system can lead to very different responses in different cells or different organisms. Studies of the mechanisms of cell signaling are leading to new understanding of many diseases, and to new strategies for therapy.

Instructions: The following problems have multiple choice answers. Correct answers are reinforced with a brief explanation. Incorrect answers are linked to tutorials to help solve the problem.


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