Chapter 11. Cell Communication.
overview of cell signaling.
Cell signaling evolved
early in the history of life.
Communicating cells may
be close together or far apart.
The three stages of cell
signaling are receptiontransduction and response.
Reception and the Initiation of Transduction.
A signal molecule binds
to a receptor protein causing the protein to change shape.
Most signal receptors
are plasma membrane proteins.
Pathways relay signals
from receptors to cellular responses.
phosphorylation, a common mode of regulation in cells is a major mechanism of
Certain small molecules
are key components of signaling pathways (second messengers).
responses to signals.
In response to a signal
a cell may regulate activities in the cytoplasm or transcription in the
amplify and specify the cells response to signals.
Overview of Cell Signaling.
Cell signaling evolved
early in the history of life.
One topic of
cell conversation is sex.
Research has found that the yeast Saccharomyces
cerevisiae identify mates via chemical signaling (Fig 11.1).
Cells of mating type a secrete a chemical signal
called a factor, while a cells secrete a factor.
These factors bind to
receptors on the opposite cell type.
The interaction of
factor and receptor cause the cells to grow towards each other without the
factor actually entering the cell.
The cells eventually
fuse (fusion or mating) combines the genes of the separate cells.
does the mating signal at the yeast cell surface bring about a cellular
The process by which a
signal on the cell surface is converted into a specific cellular response is a
series of steps called a signal-transduction pathway (STP).
Many STPs exist and have been studied in yeast and
mammals, furthermore they have been found to be strikingly similar (also
similarities in plants and bacteria). Indicates?
cells may be close together or far apart (Fig 11.3).
regulators are used by a multicellular organisms cells to influence cells
in the vicinity.
Paracrine signaling involves releasing molecules into the extracellular space to influence
many cells in the area.
Synaptic signaling (used in the nervous system) uses a neurotransmitter released
into a synapse, the narrow space between the transmitting cell and the
animals use hormones for long-distance signaling.
Specialized endocrine cells secrete hormones into
bodily fluid (Ex: blood or other vessels).
also communicate by direct contact through cell junctions or cell-cell
recognition (Fig 11.4).
three stages of cell signaling are reception, transduction and response.
Sutherland and his colleagues at Vanderbilt Univ. were pioneers in research
leading to our current understanding of how chemical messengers act via
signal-transduction pathways (Nobel Prize 1971).
Studied how the animal hormone epinephrine
stimulated glycogen (storage carbohydrate) breakdown.
They found that intact cells were necessary for
epinephrine to act and that the cells plasma membrane was somehow involved.
early work indicated the process going on at the receiving end of a cellular
conversation can be dissected into three stages: Reception, transduction
Is the targets cells detection of an incoming signal; detection is usually via
the signal binding to a protein (receptor) at the target cells surface.
Binding of the signal molecule changes the receptor protein in some way; the
transduction stage converts the signal to a form that can cause a cellular
response (often occurs over multiple steps, a signal-transduction pathway).
Transduced signal triggers a cellular response, could be any imaginable
cellular process (Ex: ?).
Reception and the Initiation of Transduction.
receptors act as identity tags on cells so that only intended target cells will
hear the message (chemical).
signal molecule binds to a receptor protein, causing the protein to change
has a specific shape that is complementary in shape to a specific signal
the signal molecule (ligand binding) to the receptor (lock and key)
causes the receptor to undergo a change in conformation (shape).
shape change often directly activates the receptor to interact with another
molecule often inside or associated with the target cell.
signal receptors are plasma membrane proteins.
molecules are are water soluble and too large to pass easily through the plasma
mating factors most signal molecules bind specific sites on receptor proteins
that are embedded in the cells plasma membrane.
Such a receptor
transmits information from the extracellular to intracellular environments by
changing shape or interacting with other molecules.
types: G-protein-linked receptors, tyrosine-kinase receptors and ion-channel
receptors are plasma membrane receptors that work with the help of a
protein called a G protein.
include yeast mating factor receptors, epinephrine receptor and other hormone and
proteins have many different receptors for different signals they each have
seven a helices spanning the membrane (Fig
protein is loosely attached to the cytoplasmic side of the membrane.
The G protein functions as a switch that is on or off
depending on which of two guanine nucleotides are attached (GTP on, GDP off).
Function (Fig 11.7):
Causes G protein to bind a GTP displacing GDP, G protein is active.
3) G protein binds
another protein, usually an enzyme activating it.
4) This activated enzyme
can trigger the next step in the pathway.
receptors (TKR) are important for activating more than one signal at one
These receptors have their own enzymatic activity,
they act as a tyrosine-kinase.
tyrosine-kinase transfers a phosphate group from ATP to the amino acid tyrosine
on a substrate protein.
TKR often have only a single a-helix spanning the membrane and an intracellular tail containing a
number of tyrosine residues.
Receptor Activation occurs in two steps (Fig 11.8):
1) Ligand binds and
causes two receptors to aggregate forming a dimer.
Aggregation activates the tyrosine-kinase portions of both receptors and they
then add phosphates to the other tails tyrosines (receptor is now fully
3) Relay proteins then
bind the phosphorylated tyrosines and are activated (10+ may be
4) These activated relay
proteins may trigger many different transduction pathways and cellular
membrane receptors of chemical signals are ligand-gated ion channel
which are pores that open or close in response to a chemical signal (Fig 11.9).
This allows the entrance or blocks the entrance of
ions like Na+ or Ca2+.
These channel proteins
bind a signal molecule as a ligand which leads to a shape change and
immediately allows ions to move in or out.
immediately changes cell function (Ex: electrical impulses of the nervous
receptors are not membrane proteins but can be dissolved in the cytosol or
nucleus of target cells.
The chemical messenger must be able to pass through
the target cell membrane to reach these receptors.
One example: Testosterone travels through the blood
and enters cells throughout the body, target cells contain receptor molecules
for testosterone in their cytoplasm.
The hormone-receptor complex enters the nucleus and
turns on specific genes that control male sex characteristics.
transduction is often a multistep process, which often amplifies the signal
leading to a large cellular response.
provide more opportunities for coordination and regulation that simpler systems
relay signals from receptors to cellular responses.
pathways act like falling dominoes, the activated receptor activates another
protein which in turn activates another and so on until the protein pathway
produces the final cellular response.
Remember the original chemical signal often never even
enters the cell it usually just activates the receptor.
this activation, conformational change is brought about by phosphorylation.
Phosphorylation, a common mode of regulation in cells, is a major mechanism of
name for a protein that transfers a phosphate from ATP to a protein is a protein
Cytoplasmic kinases act most often on other proteins
not themselves also often phosphorylate serine or threonine
residues not tyrosine (unlike receptor kinases).
Many of the relay molecules in a signal-transduction
pathway are kinases, and often act in concert (Fig 11.11).
Ex: Fig. 11.11 is
similar to that used by yeast mating factors.
Phosphorylation often activates proteins (enzymes),
however, in some cases it also can deactivate proteins.
A full 1% of all our genes are thought to be kinases and are frequently
indicted in causing cancer when they are out of control.
The cell must also be able to turn off the signal
(turning off the signal-transduction pathway), this is carried out by the protein
Protein phosphatases can rapidly remove phosphates from a protein
deactivating them, these predominate over kinases when there is no chemical
small molecules and ions are key components of signaling pathways (second
components of STPs are proteins some are small molecules or ions, called second
messengers are water soluble and therefore can rapidly spread throughout the
cell by diffusion, the two most common are Ca2+ and cyclic
AMP (cAMP; Fig 11.12).
coined the term second messenger and wanted to find the second messenger for
epinephrine-mediated glycogen breakdown.
He found cyclic adenosine monophosphate or cyclic
A transmembrane protein enzyme adenylyl cyclase
converts ATP to cAMP (Fig 11.12 and 11.13).
activates protein kinase A and the pathway continues from there.
Often associated with
and inositol triphosphate.
Many signal molecules
(Ex: neurotransmitters and growth factors) increase the intracellular
concentration of Ca2+.
Increasing the Ca2+ concentration inside of
cells can cause many responses: Muscle cell contraction, cell secretion of
certain substances, and cell division.
Ca2+ is actively pumped out of the cell and
also into the ER, and sometimes the chloroplast and mitochondria (Fig 11.14).
Therefore the Ca2+
concentration is much higher in the blood and ER than in the cytoplasm of the
response to a chemical signal the cytosolic Ca2+ concentration may
rise, by Ca2+ from the ER.
The pathway leading to Ca2+ release
involves other second messengers diacylglycerol (DAG) and inositol
after IP3 so it could be considered a third messenger.
Calcium often functions with the help of the protein calmodulin,
which binds calcium and mediates calcium-regulated processes within the cell.
Responses to Signals.
response to a signal, a cell may regulate activities in the cytoplasm or
transcription in the nucleus.
signal-transduction pathway leads to the regulation of one or more cellular
activities (Ex: change in metabolism or opening or closing a channel protein).
Ex: final step of epinephrine-mediated glycogen
breakdown pathway is the activation of the enzyme that catalyzes glycogen
signaling pathways regulate not the activity of enzymes but the synthesis
of the enzyme (Fig 11.17).
Ex: the steroid receptor acts as a transcription
factor activating gene expression in the nucleus.
Transcription factors are proteins involved in controlling the rate of
transcription for a particular gene or genes.
Elaborate pathways amplify
and specify the cells response to signals.
pathways with their multiple steps do two things amplify the signal and
add to the specificity of response (Fig 11.18).
amplification occurs due to elaborate enzyme cascades in response to a
epinephrine-induced glycogen breakdown starts with one receptor ends with 108
molecules of glucose-1-phosphate.
of cell signaling (Fig 11.18) is important because for example your
liver and heart cells are all exposed to blood (and therefore hormones) but you
only want one of them to respond to certain hormones or perhaps respond
differently to a signal ( Ex: epinephrine at the liver and heart).
How this occurs is due to the different collections of
proteins, including receptors, that cells have.
depending on the proteins available to respond to epinephrine the cell will
have a different response.
shows simplified examples (few relay molecules) signal-transduction pathways
are complex and often have many steps.
Since the cells cytosol is large in comparison to the
proteins size it would be inefficient to use diffusion for interactions
between members of a pathway instead evidence suggests scaffolding proteins
Scaffolding proteins bring one or more relay molecules into the vicinity
of an activated receptor or other activated relay molecule.
Abnormal relay proteins can lead to disorders.
Ex: Defective or missing relay protein(s) can lead to
the inherited disorder Wiskott-Aldrich syndrome (WAS) which can cause abnormal
bleeding, eczema and a predisposition to infection and leukemia.
thing to keep in mind is that the mechanisms shown in figure 11.18 also have
inhibitory mechanisms in many instances, signal transduction is a tightly