Cell Communication For cells to function in a biological system, they must communicate with other cells and respond to their external environment.

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Cell Communication For cells to function in a
biological system, they must communicate with
other cells and respond to their external
environment.
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Enduring understanding Cells communicate by
generating, transmitting and receiving chemical
signals.

• Essential knowledge
• Cell communication processes share common
  features that reflect a shared evolutionary
  history.
• Cells communicate with each other through direct
  contact with other cells or from a distance via
  chemical signaling.
• Signal transduction pathways link signal
  reception with cellular response.
• Changes in signal transduction pathways can alter
  cellular response.
• Organisms respond to changes in their external
  environments.

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Chemical Signals.

• Can direct complex processes, ranging from cell
  and organ differentiation to whole organism
  physiological responses and behaviors.
• Can allow cells to communicate without physical
  contact. The distance between the signal
  generating cell(s) and the responding cell can be
  small or large.

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Methods of cell communication

• Three general methods of cell communication
• Diffusible chemical signals (messengers) that
  travel through the organism from one location to
  another (Close or long distances)
• Physical contact between adjacent cell plasma
  membranes
• Direct cytoplasmic contact via gap junctions

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CELL COMMUNICATION
Part 1 An Overview of Cell Signaling
1.Cell signaling evolved early in the history of
life 2.Communicating cells may be close together
or far apart 3.The three stages of cell signaling
are reception, transduction, and response
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Introduction

• Cell-to-cell communication is absolutely
  essential for multicellular organisms.
• coordinate the activities within individual cells
  that support the function of the organism as a
  whole.
• Use of pheromones to trigger reproduction and
  developmental pathways
• Important for many unicellular organisms.
• finding a mate
• population density (quorum sensing)
• Response to external signals by bacteria that
  influences cell
• allowed some organisms to evolve without having a
  nervous system.

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1-Cell signaling evolved early in the history of
life

• One topic of cell conversation is mating.
• Ex The yeast Saccharomyces cerevisiae, the yeast
  of bread, wine, and beer, identifies its mates by
  chemical signaling.
• There are two sexes, a and alpha, each of which
  secretes a specific signaling molecule, a factor
  and alpha factor respectively.
• These factors each bind to receptor proteins on
  the other mating type.

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• Cell signaling has remained important in the
  microbial world.
• Myxobacteria, soil-dwelling bacteria, use
  chemical signals to communicate nutrient
  availability.
• When food is scarce, cells secrete a signal to
  other cells leading them to aggregate and form
  thick-walled spores.

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2-Communicating cells may be close together or
far apart
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Example of Localized signaling

• In synaptic signaling, a nerve cell produces the
  neurotransmitter that diffuses to a single cell
  that is almost touching the sender.

• An electrical signal passing along the nerve cell
  triggers secretion of the neurotransmitter into
  the synapse.

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2-Communicating cells may be close together or
far apart.
Touching

• Gap Junctions
• Narrow tunnels between animal cells that consist
  of proteins called connexons.
• Allows the movement of ions and small molecules
  from cell to cell.

• Plasmodesmata
• Narrow channels between plant cells
• A narrow tube of Endoplasmic reticulum.
• Material exchange

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• Cells may communicate by direct contact.
• Signaling substances dissolved in the cytosol
  pass freely between adjacent cells.

Touching

• Cells may also communicate via direct contact
  between substances on their surfaces.

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Long-Distance Signaling

• Endocrine (hormone) signaling
• Specialized cells release hormone molecules,
  which travel (usually by diffusion through cells
  or through the circulatory system) to target
  cells elsewhere in the organism

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Long-Distance Signaling

• Plants also use hormones to signal at long
  distances.

-In plants, hormones may travel in vessels, but
more often travel from cell to cell or by
diffusion in air (Ethylene). -Ethylene gas
in fruit ripening
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3. The three stages of cell signaling reception,
transduction, response

1. In reception, a chemical signal binds to a
   cellular protein, typically at the cells
   surface.
2. In transduction, binding leads to a change in the
   receptor that triggers a series of changes along
   a signal-transduction pathway.
3. In response, the transduced signal
   triggers a specific cellular activity.

McGraw-Hill Dehydration Response Example Clip
EK Signal transduction pathways link signal
reception with cellular response.
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CELL COMMUNICATION
Part 2 Signal Reception and the Initiation of
Transduction
(1) Reception A signal molecule (ligand), binds
to a receptor protein, causing the protein to
change shape
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1. A signal molecule binds to a receptor protein
causing the protein to change shape

• A cell targeted by a particular chemical signal
  has a receptor protein that recognizes the signal
  molecule.
• Recognition receptor on target cell is
  complementary in shape.
• The ligand attaches to the receptor,
  the receptor typically undergoes a
  change in shape.
• 1. This may activate the receptor so that it
  can interact
• with other molecules inside the cell.
• 2. Can lead to the aggregation of
  
• receptors.
• Signal molecule does not enter cell.

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Most signal receptors are plasma membrane proteins

• Most signal molecules are water-soluble and too
  large to pass through the plasma membrane.
• Three major types of receptors
• G-protein-linked receptors
• short for guanine nucleotide binding proteins
• Tyrosine-kinase receptors
• Ion-channel receptors

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G protein-linked receptors

• 1. G-protein-linked receptors consists of a
  receptor protein associated with a G-protein on
  the cytoplasmic side.
• The receptor consists of seven alpha helices
  spanning the membrane.
• Effective signal molecules include yeast mating
  factors, epinephrine, other hormones, and
  neurotransmitters.

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G protein-coupled receptors
G protein-linked receptors

• An example of a G protein-linked receptor is the
  epinephrine receptor.
• Epinephrine stimulates glycogen breakdown
• G-protein-linked receptors and G-proteins mediate
  a host of critical metabolic and developmental
  processes (e.g., blood vessel growth and
  development).

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G protein-linked receptors

• Uses the exchange of Guanosine diphosphate (GDP)
  for Guanosine triphosphate (GTP) as a molecular
  "switch" to allow or inhibit biochemical
  reactions inside the cell

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G protein-coupled receptors

• Large family all with 7 membrane-spanning regions

• Receptor coupled to G protein, and G protein
  stimulates effector (enzyme that promotes
  formation of intracellular second messenger)

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Guanosine triphosphate
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• The G-protein system cycles between on off.
• When a G-protein-linked receptor is activated by
  binding with an extracellular signal molecule,
  the receptor binds to an inactive G protein in
  membrane.
• This leads the G protein to substitute GTP for
  GDP.
• The G protein then binds with another membrane
  protein, often
• an enzyme,
• altering its
• activity and
• leading to a cellular response.

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• The whole system can be shut down quickly when
  the extracellular signal molecule is no longer
  present.

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G-Protein receptors

• Diseases such as diabetes and certain forms of
  pituitary cancer, among many others, are thought
  to have some root in the malfunction of G
  proteins

• G-protein receptor systems are extremely
  widespread and diverse in their functions.
• They play an important role during embryonic
  development and sensory systems.

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Ion-Channel receptors

• Ligand binding changes confirmation of the
  receptor so that specific ions can flow through
  it
• Ion movement alters the electric potential across
  the plasma membrane
• found in high numbers on neuron plasma membranes
• ligand-gated channels for sodium and potassium
• Also found on the plasma membrane of muscle cells
• binding of acetylcholine results in ion movement
  and eventual
• contraction of muscle

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• 3.Ligand-gated ion channels protein pores that
  open or close in response to a chemical signal.
• This allows or blocks ion flow, such as Na or
  Ca2.
• Binding by a ligand to the extracellular side
  changes the proteins shape and opens the
  channel.
• Ion flow changes the concentration inside the
  cell.
• When the ligand dissociates, the channel closes.

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• Ligand-gated ion channels are very important in
  the nervous system.
• EX binding of a neurotransmitter to a neuron,
  allowing the inward flow of Na2 that leads to
  the depolarization of the neuron and the
  propagation of a nervous impulse to adjacent
  cells.

                                    
This colored scanning electron micrograph shows
the synapses, or connections, between two nerve
fibers (in purple) and a nerve cell (yellow). The
picture is magnified 10,000 times.
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Way Cool Alert!

• Normally, the enzyme acetylcholinesterase
  converts acetylcholine into the inactive
  metabolites choline and acetate.
• The devastating effects of nerve agents (Sarin
  gas for example) are due to their inhibition of
  this enzyme, resulting in continuous stimulation
  of the muscles, glands and central nervous system.

• Botulinus toxin is produced by the anerobic
  bacillus Clostridium botulinum, which may be
  found in improperly canned food, and is one of
  the most potent toxins known.
• This toxin (the agent responsible for botulism)
  blocks the release of vesicles. This, of course,
  leads to muscle paralysis and, if the diaphragm
  becomes affected, can be fatal.

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Tyrosine Kinase-linked receptors
Activation Aggregation then phosphorylation

• Ligand binding results in the formation of a
  receptor dimer (2 receptors)
• The dimer then activates a class of protein
  called tyrosine
• kinases
• This activation results in the phosphorylation
  of downstream
• targets by these tyrosine kinases (stick
  phosphate groups onto
• tyrosines within the target protein)

Protein Kinases general name for an enzyme that
transfers PO4- groups from ATP to a protein
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An individual tyrosine-kinase receptor consists
of several parts

• an extracellular signal-binding sites
• a single alpha helix spanning the membrane, and
• an intracellular tail with several tyrosines.

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• When ligands bind to two receptor polypeptides,
  the polypeptides aggregate, forming a dimer.
• This activates the tyrosine-kinase section of
  both.
• These add phosphates to the tyrosine tails of the
  other polypeptide.

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• The fully-activated receptor proteins activate a
  variety of specific relay proteins that bind to
  specific phosphorylated tyrosine molecules.
• One tyrosine-kinase receptor dimer may activate
  ten or more different intracellular proteins
  simultaneously.
• These activated relay proteins trigger many
  different transduction pathways and responses.

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• The tyrosine-kinase receptor system is especially
  effective when the cell needs to regulate and
  coordinate a variety of activities and trigger
  several signal pathways at once.
• Extracellular growth factors often bind to
  tyrosine-kinase receptors.

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Insulin (Click)

• Polypeptide hormone that regulates carbohydrate
  metabolism.

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Communication through diffusion

• Other signal receptors are dissolved in the
  cytosol or nucleus of target cells.
• The signals pass through the plasma membrane.
• Include the hydrophobic steroid and thyroid
  hormones of animals.

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Action of Lipid-Soluble Hormones

• Hormone diffuses through phospholipid bilayer
  into cell
• Binds to receptor turning on/off specific genes
• Causing the synthesis of new proteins
• New proteins alters cells activity

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• Testosterone, like other hormones, travels
  through the blood and enters cells throughout the
  body.
• In the cytosol, they bind and activate receptor
  proteins.
• These activated proteins enter the nucleus and
  turn on genes that control male sex
  characteristics.

EXAMPLE
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• These activated proteins act as transcription
  factors.
• Transcription factors control which genes are
  turned on - that is, which genes are transcribed
  into messenger RNA (mRNA).
• The mRNA molecules leave the nucleus and carry
  information that directs the synthesis
  (translation) of specific proteins at the
  ribosome.

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CELL COMMUNICATION
Part 3 Signal-Transduction Pathways

• Pathways relay signals from receptors to cellular
  responses
• Protein phosphorylation, a common mode of
  regulation in cells, is a major mechanism of
  signal transduction
• Certain small molecules and ions are key
  components of signaling pathways (second
  messengers)

Insulin Signaling Clip
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Some Features of Signal-Transduction Pathways

• Secondary messengers
• Usually a multi-step pathway
• Protein phosphorylation
• Amplification (small number of signal molecules
  can produce a large cellular response)

Mr. Anderson Signal Transduction Pathways
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Pathways relay signals from receptors to cellular
responses

• Pathway acts like falling dominoes.
• The signal-activated receptor activates another
  protein, which activates another and so on, until
  the protein that produces the final cellular
  response is activated.
• The original signal molecule is not passed along
  the pathway and may not even enter the cell.
• Its information is passed on.

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Protein phosphorylation is a major mechanism of
signal transduction
phosphorylation

• The phosphorylation of proteins by a specific
  enzyme (a protein kinase) is a widespread
  cellular mechanism for regulating protein
  activity.
• Most protein kinases act on other substrate
  proteins, unlike the tyrosine kinases that act on
  themselves.

dephosphorylation
Phosphorylation is the addition of a phosphate
(PO4) group to a protein or a small molecule
Many enzymes and receptors are switched "on" or
"off" by phosphorylation and dephosphorylation.
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• Phosphorylation of a protein typically converts
  it from an inactive form to an active form.
• The reverse (inactivation) is possible too for
  some proteins.
• A single cell may have hundreds of different
  protein kinases, each specific for a different
  substrate protein.
• Fully 1 of our genes may code for protein
  kinases.
• Abnormal activity of protein kinases can cause
  abnormal cell growth and contribute to the
  development of cancer.

phosphorylation
dephosphorylation
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• Turning off a signal-transduction pathway -
  protein phosphatases.
• Rapidly remove phosphate groups from proteins.
• When an extracellular signal molecule is absent,
  active phosphatase molecules predominate, and the
  signaling pathway and cellular response are shut
  down.

ON
phosphorylation
dephosphorylation
OFF
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Certain signal molecules and ions are key
components of signaling pathways (second
messengers)

• Many signaling pathways involve small,
  nonprotein, water-soluble molecules or ions,
  called second messengers.
• These molecules rapidly diffuse throughout the
  cell.
• Two of the most important are cAMP and Ca2.
• Inositol triphosphate and GMP are others

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• Binding by epinephrine leads to increases in
  the concentration of cyclic AMP or cAMP.

cAMP

• This occurs because the receptor activates
  adenylyl cyclase, which converts ATP to cAMP.
• cAMP is short-lived as phosphodiesterase converts
  it to AMP.

McGraw-Hill Animation
Epinephrine stimulates glycogen breakdown
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cAMP -Main purpose activation of protein
kinases. -also used to regulate the passage of
Ca2 through ion channels.
cAMP
cAMP is synthesised from ATP by adenylyl cyclase.
Adenylate cyclase is located at the cell
membranes. It is activated by the hormones
glucagon and adrenaline and by G protein
cAMP controls many biological processes,
including glycogen decomposition into glucose
(glycogenolysis), and lipolysis
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• Hormones and other signals can trigger the
  formation of cAMP.
• Binding by the signal to a receptor activates a G
  protein that activates adenylyl cyclase in the
  plasma membrane.

cAMP

• The cAMP from the adenylyl cyclase diffuses
  through the cell and activates a
  serine/threonine kinase, called protein kinase A
  which phosphorylates other proteins.

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• Certain microbes cause disease by disrupting the
  G-protein signaling pathways.
• The cholera bacterium, colonizes the small
  intestine and produces a toxin that modifies a G
  protein that regulates salt and water secretion.
• The modified G protein is stuck in its active
  form, continuously stimulating productions of
  cAMP.
• This causes the intestinal cells to secrete large
  amounts of water and salts into the intestines,
  leading to profuse diarrhea and death if
  untreated.

cAMP
The toxin acts as an enzyme that changes the G
protein so that it can no longer switch itself
off
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• Many signal molecules in animals induce responses
  in their target cells via signal-transduction
  pathways that increase the cytosolic
  concentration of Ca2.
• In animal cells, increases in Ca2 may cause
  contraction of muscle cells, secretion of some
  substances, and cell division.
• In plant cells, increases in Ca2 trigger
  responses for coping with environmental stress,
  including drought.
• Cells use Ca2 as a second messenger in both
  G-protein pathways and tyrosine-kinase pathways.

Ca2.
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Other secondary messengers inositol triphosphate
(IP3)- -stimulates the release of calcium ions
from the smooth endoplasmic reticulum
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CELL COMMUNICATION
Part 4 Cellular Responses to Signals

• In response to a signal, a cell may regulate
  activities in the cytoplasm or transcription in
  the nucleus
• Elaborate pathways amplify and specify the cells
  response to signals

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In response to a signal, a cell may regulate
activities in the cytoplasm or transcription in
the nucleus

• Ultimately, a signal-transduction pathway leads
  to the regulation of one or more cellular
  activities.
• This may be a change in an ion channel or a
  change in cell metabolism.
• EX, epinephrine activates enzymes that catalyze
  the breakdown of glycogen.

click
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• The stimulation of glycogen breakdown by
  epinephrine
• involves a G-protein-
• linked receptor,
• a G Protein adenylyl cyclase and cAMP, and
  several protein kinases before glycogen
  phosphorylaseis activated.

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• Other signaling pathways do not regulate the
  activity of enzymes but the synthesis of enzymes
  or other proteins.
• Activated receptors may act as transcription
  factors that turn specific genes on or off in the
  nucleus.

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Pathways amplify and specify the cells response
to signals

• Signaling pathways with multiple steps have two
  benefits.
• They amplify the response to a signal.
• They contribute to the specificity of the
  response.
• At each catalytic step in a cascade, the number
  of activated products is much greater than in the
  preceding step.
• In the epinephrine-triggered pathway, binding by
  a small number of epinephrine molecules can lead
  to the release of hundreds of millions of glucose
  molecules.

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• Various types of cells may receive the same
  signal but produce very different responses.
• For example, epinephrine triggers liver or
  striated muscle cells to break down glycogen, but
  cardiac muscle cells are stimulated to contract,
  leading to a rapid heartbeat.
• These differences result from a basic
  observation
• Different kinds of cells have different
  collections of proteins.
• STRUCTURE AND FUNCTION.

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• The response of a particular cell to a signal
  depends on its particular collection of receptor
  proteins, relay proteins, and proteins needed to
  carry out the response.

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• As important as activating mechanisms are, we
  must say something about inactivating mechanisms.
• For a cell to remain alert and capable of
  responding to incoming signals, each molecular
  change in its signaling pathways must last only a
  short time.
• If signaling pathway components become locked
  into one state, the proper function of the cell
  can be disrupted.
• Binding of signal molecules to receptors must be
  reversible, allowing the receptors to return to
  their inactive state when the signal is released.
• Similarly, activated signals (cAMP and
  phosphorylated proteins) must be inactivated by
  appropriate enzymes to prepare the cell for a
  fresh signal.

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• Conditions where signal transduction is blocked
  or defective can be deleterious, preventative or
  prophylactic.
• Diabetes, heart disease, neurological disease,
  autoimmune disease, cancer, cholera
• Effects of neurotoxins, poisons, pesticides
  Drugs (Hypertensives, Anesthetics, Antihistamines
  and Birth Control Drugs)

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Extracellular Signaling Review

• Signaling molecules are released by signaling
  cells
• The signal is called the ligand
• The ligand binds to its specific receptor on a
  target cell
• This ligand-receptor interaction induces a
  conformational or shape-change in the receptor
• Produces a specific response - called the
  cellular response
• Can include a vast array of compounds
• e.g. small amino acid derivatives, small
  peptides, proteins

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Cell-to-cell communication by extracellular
signaling usually involves six steps

• (1) synthesis of the signaling molecule by the
  signaling cell
• (2) release of the signaling molecule by the
  signaling cell
• (3) transport of the signal to the target cell
• (4) detection of the signal by a specific
  receptor protein receptor-ligand specificity
• (5) a change in cellular metabolism, function, or
  development cellular response
• triggered by the receptor-ligand complex
  specific to the ligand-receptor complex
• (6) removal of the signal, which usually
  terminates the cellular response degredation of
  ligand