Wikipedia

Cell signaling

(Redirected fromSignaling pathway)
For the journal, seeCellular Signalling.

Inbiology,cell signaling(cell signallinginBritish English) is theprocessby which acellinteracts with itself, other cells, and the environment. Cell signaling is a fundamental property of allcellular lifeinprokaryotesandeukaryotes.

Typically, the signaling process involves three components: the signal, the receptor, and the effector.[citation needed]

In biology, signals are mostly chemical in nature, but can also be physical cues such aspressure,voltage,temperature,or light. Chemical signals are molecules with the ability to bind and activate a specificreceptor.These molecules, also referred as ligands, are chemically diverse, includingions(e.g. Na+, K+, Ca++, etc.), lipids (e.g. steroid, prostaglandin), peptides (e.g. insulin, ACTH), carbohydrates, glycosylated proteins (proteoglycans), nucleic acids, etc. Peptide and lipid ligands are particularly important, as most hormones belong to these classes of chemicals. Peptides are usually polar, hydrophilic molecules. As such they are unable to diffuse freely across the bi-lipid layer of the plasma membrane, so their action is mediated by a cell membrane bound receptor. On the other hand, liposoluble chemicals such as steroid hormones, can diffuse passively across the plasma membrane and interact with intracellular receptors. Cell signaling can occur over short or long distances, and can be further classified asautocrine,intracrine,juxtacrine,paracrine,orendocrine.Autocrine signalingoccurs when the chemical signal acts on the same cell that produced the signaling chemical.[1]Intracrine signaling occurs when the chemical signal produced by a cell acts on receptors located in the cytoplasm or nucleus of the same cell.[2]Juxtacrine signaling occurs between physically adjacent cells.[3]Paracrine signaling occurs between nearby cells. Endocrine interaction occurs between distant cells, with the chemical signal usually carried by the blood.[4]

Receptorsare complex proteins or tightly bound multimer of proteins, located in the plasma membrane or within the interior of the cell such as in thecytoplasm,organelles,andnucleus.Receptors have the ability to detect a signal either by binding to a specific chemical or by undergoing a conformational change when interacting with physical agents. It is the specificity of the chemical interaction between a given ligand and its receptor that confers the ability to trigger a specific cellular response. Receptors can be broadly classified into cell membrane receptors and intracellular receptors.

Cell membrane receptorscan be further classified into ion channel linked receptors, G-Protein coupled receptors and enzyme linked receptors.

Ion channels receptors are large transmembrane proteins with a ligand activated gate function. When these receptors are activated, they may allow or block passage of specific ions across the cell membrane. Most receptors activated by physical stimuli such as pressure or temperature belongs to this category.

G-protein receptorsare multimeric proteins embedded within the plasma membrane. These receptors have extracellular, trans-membrane and intracellular domains. The extracellular domain is responsible for the interaction with a specific ligand. The intracellular domain is responsible for the initiation of a cascade of chemical reactions which ultimately triggers the specific cellular function controlled by the receptor.

Enzyme-linked receptorsaretransmembrane proteinswith an extracellular domain responsible for binding a specific ligand and an intracellular domain with enzymatic or catalytic activity. Upon activation the enzymatic portion is responsible for promoting specific intracellular chemical reactions.

Intracellular receptorshave a different mechanism of action. They usually bind to lipid soluble ligands that diffuse passively through the plasma membrane such as steroid hormones. These ligands bind to specific cytoplasmic transporters that shuttle the hormone-transporter complex inside the nucleus where specific genes are activated and the synthesis of specific proteins is promoted.

The effector component of the signaling pathway begins withsignal transduction.In this process, the signal, by interacting with the receptor, starts a series of molecular events within the cell leading to the final effect of the signaling process. Typically the final effect consists in the activation of an ion channel (ligand-gated ion channel) or the initiation of asecond messenger systemcascade that propagates the signal through the cell. Second messenger systems can amplify or modulate a signal, in which activation of a few receptors results in multiple secondary messengers being activated, thereby amplifying the initial signal (the first messenger). Thedownstream effectsof these signaling pathways may include additional enzymatic activities such asproteolytic cleavage,phosphorylation,methylation,andubiquitinylation.

Signaling molecules can be synthesized from various biosynthetic pathways and released throughpassiveoractive transports,or even fromcell damage.

Each cell is programmed to respond to specific extracellular signal molecules, and is the basis ofdevelopment,tissue repair,immunity,andhomeostasis.Errors in signaling interactions may cause diseases such ascancer,autoimmunity,anddiabetes.

Taxonomic range

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In many small organisms such asbacteria,quorum sensingenables individuals to begin an activity only when the population is sufficiently large. This signaling between cells was first observed in the marine bacteriumAliivibrio fischeri,whichproduces lightwhen the population is dense enough.[5]The mechanism involves the production and detection of a signaling molecule, and the regulation of gene transcription in response. Quorum sensing operates in both gram-positive and gram-negative bacteria, and both within and between species.[6]

Inslime molds,individual cells aggregate together to form fruiting bodies and eventually spores, under the influence of a chemical signal, known as anacrasin.The individuals move bychemotaxis,i.e. they are attracted by the chemical gradient. Some species usecyclic AMPas the signal; others such asPolysphondylium violaceumuse adipeptideknown asglorin.[7]

In plants and animals, signaling between cells occurs either through release into theextracellular space,divided inparacrine signaling(over short distances) andendocrine signaling(over long distances), or by direct contact, known asjuxtacrine signalingsuch asnotch signaling.[8]Autocrine signalingis a special case of paracrine signaling where the secreting cell has the ability to respond to the secreted signaling molecule.[9]Synapticsignaling is a special case of paracrine signaling (forchemical synapses) or juxtacrine signaling (forelectrical synapses) betweenneuronsand target cells.

Extracellular signal

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Synthesis and release

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Different types of extracellular signaling

Many cell signals are carried by molecules that are released by one cell and move to make contact with another cell. Signaling molecules can belong to several chemical classes:lipids,phospholipids,amino acids,monoamines,proteins,glycoproteins,orgases.Signaling molecules binding surface receptors are generally large andhydrophilic(e.g.TRH,Vasopressin,Acetylcholine), while those entering the cell are generally small andhydrophobic(e.g.glucocorticoids,thyroid hormones,cholecalciferol,retinoic acid), but important exceptions to both are numerous, and the same molecule can act both via surface receptors or in an intracrine manner to different effects.[9]In animal cells, specialized cells release these hormones and send them through the circulatory system to other parts of the body. They then reach target cells, which can recognize and respond to the hormones and produce a result. This is also known as endocrine signaling. Plant growth regulators, or plant hormones, move through cells or by diffusing through the air as a gas to reach their targets.[10]Hydrogen sulfideis produced in small amounts by some cells of the human body and has a number of biological signaling functions. Only two other such gases are currently known to act as signaling molecules in the human body:nitric oxideandcarbon monoxide.[11]

Exocytosis

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Exocytosisis the process by which a cell transportsmoleculessuch asneurotransmittersandproteinsout of the cell. As anactive transportmechanism, exocytosis requires the use of energy to transport material. Exocytosis and its counterpart,endocytosis,the process that brings substances into the cell, are used by all cells because mostchemical substancesimportant to them are largepolarmolecules that cannot pass through thehydrophobicportion of thecell membranebypassive transport.Exocytosis is the process by which a large amount of molecules are released; thus it is a form of bulk transport. Exocytosis occurs via secretory portals at the cell plasma membrane calledporosomes.Porosomes are permanent cup-shaped lipoprotein structures at the cell plasma membrane, where secretory vesicles transiently dock and fuse to release intra-vesicular contents from the cell.[12]

In exocytosis, membrane-bound secretoryvesiclesare carried to thecell membrane,where they dock and fuse at porosomes and their contents (i.e., water-soluble molecules) are secreted into the extracellular environment. Thissecretionis possible because the vesicle transientlyfuseswith the plasma membrane. In the context ofneurotransmission,neurotransmitters are typically released fromsynaptic vesiclesinto thesynaptic cleftvia exocytosis; however, neurotransmitters can also be released viareverse transportthroughmembrane transport proteins.[citation needed]

Forms of Cell Signaling

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Autocrine

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Differences between autocrine and paracrine signaling

Autocrine signaling involves a cell secreting a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on that same cell, leading to changes in the cell itself.[13]This can be contrasted withparacrine signaling,intracrinesignaling, or classicalendocrinesignaling.

Intracrine

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In intracrine signaling, the signaling chemicals are produced inside the cell and bind to cytosolic or nuclear receptors without being secreted from the cell.. In intracrine signaling, signals are relayed without being secreted from the cell. The intracrine signals not being secreted outside of the cell is what sets apart intracrine signaling from the other cell signaling mechanisms such as autocrine signaling. In both autocrine and intracrine signaling, the signal has an effect on the cell that produced it.[14]

Juxtacrine

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Juxtacrine signaling is a type ofcell–cell or cell–extracellular matrixsignaling inmulticellularorganisms that requires close contact. There are three types:

This image displays the different types of cell signaling
  1. A membraneligand(protein,oligosaccharide,lipid) and amembrane proteinof two adjacent cellsinteract.
  2. A communicatingjunctionlinks the intracellular compartments of two adjacent cells, allowing transit of relatively small molecules.
  3. Anextracellular matrixglycoproteinand a membrane protein interact.

Additionally, inunicellularorganisms such asbacteria,juxtacrine signaling means interactions by membrane contact. Juxtacrine signaling has been observed for somegrowth factors,cytokineandchemokinecellular signals, playing an important role in theimmune response.Juxtacrine signalling via direct membrane contacts is also present between neuronal cell bodies and motile processes ofmicrogliaboth during development,[15]and in the adult brain.[16]

Paracrine

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In paracrine signaling, a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as paracrine factors diffuse over a relatively short distance (local action), as opposed to cell signaling byendocrine factors,hormones which travel considerably longer distances via thecirculatory system;juxtacrine interactions;andautocrine signaling.Cells that produce paracrine factors secrete them into the immediateextracellularenvironment. Factors then travel to nearby cells in which the gradient of factor received determines the outcome. However, the exact distance that paracrine factors can travel is not certain.

Paracrinesignals such asretinoic acidtarget only cells in the vicinity of the emitting cell.[17]Neurotransmittersrepresent another example of a paracrine signal.

Some signaling molecules can function as both a hormone and a neurotransmitter. For example,epinephrineandnorepinephrinecan function as hormones when released from theadrenal glandand are transported to the heart by way of the blood stream. Norepinephrine can also be produced byneuronsto function as a neurotransmitter within the brain.[18]Estrogencan be released by theovaryand function as a hormone or act locally via paracrine orautocrinesignaling.[19]

Although paracrine signaling elicits a diverse array of responses in the induced cells, most paracrine factors utilize a relatively streamlined set ofreceptorsand pathways. In fact, differentorgansin the body - even between different species - are known to utilize a similar sets of paracrine factors in differential development.[20]The highly conserved receptors and pathways can be organized into four major families based on similar structures:fibroblast growth factor(FGF) family,Hedgehogfamily,Wntfamily, andTGF-β superfamily.Binding of a paracrine factor to its respective receptor initiatessignal transductioncascades, eliciting different responses.

Endocrine

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Endocrinesignals are calledhormones.Hormones are produced by endocrine cells and they travel through thebloodto reach all parts of the body. Specificity of signaling can be controlled if only some cells can respond to a particular hormone. Endocrine signaling involves the release ofhormonesby internalglandsof anorganismdirectly into thecirculatory system,regulating distant target organs. Invertebrates,thehypothalamusis the neural control center for all endocrine systems. Inhumans,the majorendocrine glandsare thethyroid glandand theadrenal glands.The study of the endocrine system and its disorders is known asendocrinology.

Receptors

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Main article:Receptor (biochemistry)
Transmembrane receptor working principle

Cells receive information from their neighbors through a class of proteins known asreceptors.Receptors may bind with some molecules (ligands) or may interact with physical agents like light, mechanical temperature, pressure, etc. Reception occurs when the target cell (any cell with areceptor proteinspecific to thesignal molecule) detects a signal, usually in the form of a small, water-soluble molecule, via binding to a receptor protein on the cell surface, or once inside the cell, the signaling molecule can bind tointracellular receptors,other elements, or stimulateenzymeactivity (e.g. gasses), as in intracrine signaling.

Signaling molecules interact with a target cell as aligandtocell surface receptors,and/or by entering into the cell through itsmembraneorendocytosisforintracrinesignaling. This generally results in the activation ofsecond messengers,leading to various physiological effects. In many mammals, earlyembryocells exchange signals with cells of theuterus.[21]In the humangastrointestinal tract,bacteriaexchange signals with each other and with humanepithelialandimmune systemcells.[22]For the yeastSaccharomyces cerevisiaeduringmating,some cells send apeptidesignal (mating factorpheromones) into their environment. The mating factor peptide may bind to a cell surfacereceptoron other yeast cells and induce them to prepare for mating.[23]

Cell surface receptors

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See also:Ligand (biochemistry)andReceptor–ligand kinetics

Cell surface receptors play an essential role in the biological systems of single- and multi-cellular organisms and malfunction or damage to these proteins is associated with cancer, heart disease, and asthma.[24]Thesetrans-membranereceptors are able to transmit information from outside the cell to the inside because theychange conformationwhen a specific ligand binds to it. There are three major types:Ion channel linked receptors,G protein–coupled receptors,andenzyme-linked receptors.

Ion channel linked receptors

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The AMPA receptor bound to a glutamate antagonist showing the amino terminal, ligand binding, and transmembrane domain, PDB 3KG2

Ion channel linked receptors are a group oftransmembraneion-channelproteins which open to allow ions such asNa+,K+,Ca2+,and/orCl−to pass through the membrane in response to the binding of a chemical messenger (i.e. aligand), such as aneurotransmitter.[25][26][27]

When apresynaptic neuronis excited, it releases aneurotransmitterfrom vesicles into thesynaptic cleft.The neurotransmitter then binds to receptors located on thepostsynaptic neuron.If these receptors are ligand-gated ion channels, a resulting conformational change opens the ion channels, which leads to a flow of ions across the cell membrane. This, in turn, results in either adepolarization,for an excitatory receptor response, or ahyperpolarization,for an inhibitory response.

These receptor proteins are typically composed of at least two different domains: a transmembrane domain which includes the ion pore, and an extracellular domain which includes the ligand binding location (anallostericbinding site). This modularity has enabled a 'divide and conquer' approach to finding the structure of the proteins (crystallising each domain separately). The function of such receptors located atsynapsesis to convert the chemical signal ofpresynapticallyreleased neurotransmitter directly and very quickly into apostsynapticelectrical signal. Many LICs are additionally modulated byallostericligands,bychannel blockers,ions,or themembrane potential.LICs are classified into three superfamilies which lack evolutionary relationship:cys-loop receptors,ionotropic glutamate receptorsandATP-gated channels.

G protein–coupled receptors

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A G Protein-coupled receptor within the plasma membrane

G protein-coupled receptors are a large group ofevolutionarily-related proteinsthat arecell surface receptorsthat detectmoleculesoutside thecelland activate cellular responses. Coupling withG proteins,they are called seven-transmembrane receptors because they pass through thecell membraneseven times. The G-protein acts as a "middle man" transferring the signal from its activated receptor to its target and therefore indirectly regulates that target protein.[28]Ligands can bind either to extracellular N-terminus and loops (e.g. glutamate receptors) or to the binding site within transmembrane helices (Rhodopsin-like family). They are all activated byagonistsalthough a spontaneous auto-activation of an empty receptor can also be observed.[28]

G protein-coupled receptors are found only ineukaryotes,includingyeast,choanoflagellates,[29]and animals. Theligandsthat bind and activate these receptors include light-sensitive compounds,odors,pheromones,hormones,andneurotransmitters,and vary in size from small molecules topeptidesto largeproteins.G protein-coupled receptors are involved in many diseases.

There are two principal signal transduction pathways involving the G protein-coupled receptors:cAMPsignal pathway andphosphatidylinositolsignal pathway.[30]When a ligand binds to the GPCR it causes a conformational change in the GPCR, which allows it to act as aguanine nucleotide exchange factor(GEF). The GPCR can then activate an associatedG proteinby exchanging theGDPbound to the G protein for aGTP.The G protein's α subunit, together with the bound GTP, can then dissociate from the β and γ subunits to further affect intracellular signaling proteins or target functional proteins directly depending on the α subunit type (Gαs,Gαi/o,Gαq/11,Gα12/13).[31]: 1160 

G protein-coupled receptors are an important drug target and approximately 34%[32]of all Food and Drug Administration (FDA) approved drugs target 108 members of this family. The global sales volume for these drugs is estimated to be 180 billion US dollars as of 2018.[32]It is estimated that GPCRs are targets for about 50% of drugs currently on the market, mainly due to their involvement in signaling pathways related to many diseases i.e. mental, metabolic including endocrinological disorders, immunological including viral infections, cardiovascular, inflammatory, senses disorders, and cancer. The long ago discovered association between GPCRs and many endogenous and exogenous substances, resulting in e.g. analgesia, is another dynamically developing field of pharmaceutical research.[28]

Enzyme-linked receptors

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VEGF receptors are a type of enzyme-coupled receptors, specifically tyrosine kinase receptors

Enzyme-linked receptors (or catalytic receptors) aretransmembrane receptorsthat, upon activation by an extracellularligand,causesenzymaticactivity on the intracellular side.[33]Hence a catalytic receptor is anintegral membrane proteinpossessing bothenzymatic,catalytic,andreceptorfunctions.[34]

They have two important domains, an extra-cellular ligand binding domain and an intracellular domain, which has a catalytic function; and a singletransmembrane helix.The signaling molecule binds to the receptor on the outside of the cell and causes a conformational change on the catalytic function located on the receptor inside the cell.[citation needed]Examples of the enzymatic activity include:

Intracellular receptors

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Intracellular receptors exist freely in the cytoplasm, nucleus, or can be bound to organelles or membranes. For example, the presence of nuclear and mitochondrial receptors is well documented.[36]The binding of a ligand to the intracellular receptor typically induces a response in the cell. Intracellular receptors often have a level of specificity, this allows the receptors to initiate certain responses when bound to a corresponding ligand.[37]Intracellular receptors typically act on lipid soluble molecules. The receptors bind to a group of DNA binding proteins. Upon binding, the receptor-ligand complex translocates to the nucleus where they can alter patterns of gene expression.[38]

Steroid hormone receptor

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Main article:Steroid hormone receptor

Steroid hormone receptors are found in thenucleus,cytosol,and also on theplasma membraneof target cells. They are generallyintracellular receptors(typically cytoplasmic or nuclear) and initiatesignal transductionforsteroid hormoneswhich lead to changes in gene expression over a time period of hours to days. The best studied steroid hormonereceptorsare members of thenuclear receptorsubfamily 3 (NR3) that include receptors forestrogen(group NR3A)[39]and 3-ketosteroids (group NR3C).[40]In addition to nuclear receptors, severalG protein-coupled receptorsandion channelsact ascell surface receptorsfor certain steroid hormones.

Mechanisms of Receptor Down-Regulation

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Receptor mediated endocytosisis common way of turning receptors "off". Endocytic down regulation is regarded as a means for reducing receptor signaling.[41]The process involves the binding of a ligand to the receptor, which then triggers the formation of coated pits, the coated pits transform to coated vesicles and are transported to the endosome.

Receptor Phosphorylation is another type of receptor down-regulation. Biochemical changes can reduce receptor affinity for a ligand.[42]

Reducing the sensitivity of the receptor is a result of receptors being occupied for a long time. This results in a receptor adaptation in which the receptor no longer responds to the signaling molecule. Many receptors have the ability to change in response to ligand concentration.[43]

Signal transduction pathways

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Further information:Signal transductionandList of signalling pathways

When binding to the signaling molecule, the receptor protein changes in some way and starts the process of transduction, which can occur in a single step or as a series of changes in a sequence of different molecules (called a signal transduction pathway). The molecules that compose these pathways are known as relay molecules. The multistep process of the transduction stage is often composed of the activation of proteins by addition or removal of phosphate groups or even the release of other small molecules or ions that can act as messengers. The amplifying of a signal is one of the benefits to this multiple step sequence. Other benefits include more opportunities for regulation than simpler systems do and the fine-tuning of the response, in both unicellular and multicellular organism.[10]

In some cases, receptor activation caused by ligand binding to a receptor is directly coupled to the cell's response to the ligand. For example, the neurotransmitterGABAcan activate a cell surface receptor that is part of anion channel.GABA binding to aGABAAreceptoron a neuron opens achloride-selective ion channel that is part of the receptor. GABAAreceptor activation allows negatively charged chloride ions to move into the neuron, which inhibits the ability of the neuron to produceaction potentials.However, for many cell surface receptors, ligand-receptor interactions are not directly linked to the cell's response. The activated receptor must first interact with other proteins inside the cell before the ultimatephysiologicaleffect of the ligand on the cell's behavior is produced. Often, the behavior of a chain of several interacting cell proteins is altered following receptor activation. The entire set of cell changes induced by receptor activation is called asignal transductionmechanism or pathway.[44]

Key components of a signal transduction pathway (MAPK/ERK pathwayshown)

A more complex signal transduction pathway is the MAPK/ERK pathway, which involves changes ofprotein–protein interactionsinside the cell, induced by an external signal. Many growth factors bind to receptors at the cell surface and stimulate cells to progress through thecell cycleanddivide.Several of these receptors arekinasesthat start to phosphorylate themselves and other proteins when binding to a ligand. Thisphosphorylationcan generate a binding site for a different protein and thus induce protein–protein interaction. In this case, the ligand (calledepidermal growth factor,or EGF) binds to the receptor (calledEGFR). This activates the receptor to phosphorylate itself. The phosphorylated receptor binds to anadaptor protein(GRB2), which couples the signal to further downstream signaling processes. For example, one of the signal transduction pathways that are activated is called themitogen-activated protein kinase(MAPK) pathway. The signal transduction component labeled as "MAPK" in the pathway was originally called "ERK," so the pathway is called theMAPK/ERK pathway.The MAPK protein is an enzyme, aprotein kinasethat can attachphosphateto target proteins such as thetranscription factorMYCand, thus, alter gene transcription and, ultimately, cell cycle progression. Many cellular proteins are activated downstream of the growth factor receptors (such as EGFR) that initiate this signal transduction pathway.[citation needed]

Some signaling transduction pathways respond differently, depending on the amount of signaling received by the cell. For instance, thehedgehog proteinactivates different genes, depending on the amount of hedgehog protein present.[citation needed]

Complex multi-component signal transduction pathways provide opportunities for feedback, signal amplification, and interactions inside one cell between multiple signals and signaling pathways.[citation needed]

A specific cellular response is the result of the transduced signal in the final stage of cell signaling. This response can essentially be any cellular activity that is present in a body. It can spur the rearrangement of the cytoskeleton, or even as catalysis by an enzyme. These three steps of cell signaling all ensure that the right cells are behaving as told, at the right time, and in synchronization with other cells and their own functions within the organism. At the end, the end of a signal pathway leads to the regulation of a cellular activity. This response can take place in the nucleus or in the cytoplasm of the cell. A majority of signaling pathways control protein synthesis by turning certain genes on and off in the nucleus. [45]

In unicellular organisms such as bacteria, signaling can be used to 'activate' peers from adormant state,enhancevirulence,defend againstbacteriophages,etc.[46]Inquorum sensing,which is also found in social insects, the multiplicity of individual signals has the potentiality to create a positive feedback loop, generating coordinated response. In this context, the signaling molecules are calledautoinducers.[47][48][49]This signaling mechanism may have been involved inevolutionfrom unicellular to multicellular organisms.[47][50]Bacteria also use contact-dependent signaling, notably to limit their growth.[51]

Signaling molecules used by multicellular organisms are often calledpheromones.They can have such purposes as alerting against danger, indicating food supply, or assisting in reproduction.[52]

Short-term cellular responses

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Brief overview of some signaling pathways (based on receptor families) that result in short-acting cellular responses
Receptor Family Example of Ligands/ activators (Bracket: receptor for it) Example ofeffectors Further downstream effects
Ligand Gated Ion Channels Acetylcholine
(such asNicotinic acetylcholine receptor), 		Changes in membrane permeability Change in membrane potential
Seven Helix Receptor Light (Rhodopsin),
Dopamine(Dopamine receptor),
GABA(GABA receptor),
Prostaglandin(prostaglandin receptor) etc. 		TrimericG protein Adenylate Cyclase,
cGMP phosphodiesterase,
G-protein gated ion channel,etc.
Two-component Diverse activators Histidine Kinase Response Regulator - flagellar movement, Gene expression
Membrane Guanylyl Cyclase Atrial natriuretic peptide,
Sea urchin egg peptide etc. 		cGMP Regulation of Kinases and channels- Diverse actions
Cytoplasmic Guanylyl cyclase Nitric Oxide(Nitric oxide receptor) cGMP Regulation of cGMP Gated channels, Kinases
Integrins Fibronectins,other extracellular matrix proteins Nonreceptor tyrosine kinase Diverse response

.[53][54]

Regulating gene activity

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Signal transduction pathways that lead to a cellular response
Brief overview of some signaling pathways (based on receptor families) that control gene activity
Frizzled(special type of 7Helix receptor) Wnt Dishevelled,axin - APC, GSK3-beta - Beta catenin Gene expression
Two-component Diverse activators Histidine Kinase Response Regulator - flagellar movement, Gene expression
Receptor Tyrosine Kinase Insulin(insulin receptor),
EGF(EGF receptor),
FGF-Alpha, FGF-Beta, etc. (FGF-receptors) 		Ras,MAP-kinases,PLC,PI3-Kinase Gene expression change
Cytokine receptors Erythropoietin,
Growth Hormone(Growth Hormone Receptor),
IFN-Gamma(IFN-Gamma receptor) etc. 		JAK kinase STAT transcription factor- Gene expression
Tyrosine kinase Linked- receptors MHC-peptide complex - TCR, Antigens - BCR Cytoplasmic Tyrosine Kinase Gene expression
Receptor Serine/Threonine Kinase Activin(activin receptor),
Inhibin,
Bone-morphogenetic protein(BMP Receptor),
TGF-beta 		Smadtranscription factors Control of gene expression
Sphingomyelinase linked receptors IL-1(IL-1 receptor),
TNF(TNF-receptors) 		Ceramide activated kinases Gene expression
Cytoplasmic Steroid receptors Steroid hormones,
Thyroid hormones,
Retinoic acidetc. 		Work as/ interact with transcription factors Gene expression

.[53][54]

Notch signaling pathway

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Notch-mediated juxtacrine signal between adjacent cells

Notchis a cell surface protein that functions as a receptor. Animals have a small set ofgenesthat code for signaling proteins that interact specifically with Notch receptors and stimulate a response in cells that express Notch on their surface. Molecules that activate (or, in some cases, inhibit) receptors can be classified as hormones,neurotransmitters,cytokines,andgrowth factors,in general calledreceptor ligands.Ligand receptor interactions such as that of the Notch receptor interaction, are known to be the main interactions responsible for cell signaling mechanisms and communication.[55]notchacts as a receptor for ligands that are expressed on adjacent cells. While some receptors are cell-surface proteins, others are found inside cells. For example,estrogenis ahydrophobicmolecule that can pass through thelipid bilayerof themembranes.As part of theendocrine system,intracellularestrogen receptorsfrom a variety of cell types can be activated by estrogen produced in theovaries.[citation needed]

In the case of Notch-mediated signaling, the signal transduction mechanism can be relatively simple. As shown in Figure 2, the activation of Notch can cause the Notch protein to be altered by aprotease.Part of the Notch protein is released from the cell surface membrane and takes part ingene regulation.Cell signaling research involves studying the spatial and temporal dynamics of both receptors and the components of signaling pathways that are activated by receptors in various cell types.[56][57]Emerging methods for single-cell mass-spectrometry analysis promise to enable studying signal transduction with single-cell resolution.[58]

Innotch signaling,direct contact between cells allows for precise control of celldifferentiationduring embryonic development. In the wormCaenorhabditis elegans,two cells of the developinggonadeach have an equal chance of terminally differentiating or becoming a uterine precursor cell that continues to divide. The choice of which cell continues to divide is controlled by competition of cell surface signals. One cell will happen to produce more of a cell surface protein that activates the Notchreceptoron the adjacent cell. This activates afeedback loopor system that reduces Notch expression in the cell that will differentiate and that increases Notch on the surface of the cell that continues as astem cell.[59]

See also

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References

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Further reading

edit
  • "The Inside Story of Cell Communication".learn.genetics.utah.edu.Retrieved 2018-10-20.
  • "When Cell Communication Goes Wrong".learn.genetics.utah.edu.Retrieved 2018-10-24.
edit
Retrieved from "https://en.wikipedia.org/w/index.php?title=Cell_signaling&oldid=1256894497#Signaling_pathways"