Response: Cell signaling
leads to regulation of
transcription or cytoplasmic
activities
Chapter 11.4
Growth factor
Reception
Receptor
Nuclear and Cytoplasmic
Responses
Phosphorylation
cascade

Ultimately, a signal transduction pathway leads
to regulation of one or more cellular activities.

The response may occur in the cytoplasm or in
the nucleus.

Many signaling pathways regulate the synthesis
of enzymes or other proteins, usually by turning
genes on or off in the nucleus.

The final activated molecule in the signaling
pathway may function as a transcription factor.
Transduction
CYTOPLASM
Inactive
transcription
factor
Active
transcription
factor
P
Response
DNA
Gene
NUCLEUS
mRNA

Other pathways regulate the activity of enzymes rather than their
synthesis.

This directly affects proteins that function outside the nucleus.

Example: a signal may cause the opening or closing of an ion channel in
the plasma membrane or a change in cell metabolism.

Signaling pathways can also affect the overall behavior of a cell, for
example, changes in cell shape

Some pathways lead to cell division.

The molecular messengers that initiate cell division pathways include
growth factors and certain plan and animal hormones.

Malfunctioning of growth factor pathways may lead to cancer.
Fine-Tuning of the Response

Whether the response occurs in the nucleus or in the cytoplasm, it is
not simply turned “on” or “off.”

There are four aspects of fine-tuning to consider:

Amplification of the signal (and thus the response)

Specificity of the response

Overall efficiency of response, enhanced by scaffolding proteins

Termination of the signal
Signal Amplification

Enzyme cascades amplify the cell’s response.

At each catalytic step in the cascade, the
number of activated products can be much
greater than in the preceding step.

The amplification effect stems from the fact
that these proteins persist in the active form
long enough to process multiple molecules of
substrate before they become inactive again.

Example: Epinephrine

When epinephrine binds to a receptor on liver
or muscle cell, glycogen is broken down into
glucose.

A small number of epinephrine molecules
binding to receptors on liver cell or muscle
cell can lead to hundreds of millions of
glucose molecules from glycogen.
The Specificity of Cell Signaling and Coordination of
the Response

Different kinds of cells have different collections of proteins.

These different proteins allow cells to detect and respond to different signals.

Even the same signal can have different effects in cells with different
proteins and pathways.
Signaling
molecule
Receptor
Relay
molecules
Response 1
Cell A. Pathway leads
to a single response.
Activation
or inhibition
Response 2
Response 3
Cell B. Pathway branches,
leading to two responses.
Response 4
Cell C. Cross-talk occurs
between two pathways.
Response 5
Cell D. Different receptor
leads to a different
response.
Signaling Efficiency: Scaffolding Proteins
and Signaling Complexes

Scaffolding proteins are large relay proteins to which other relay proteins are
attached.

Scaffolding proteins can increase the signal transduction efficiency by
grouping together different proteins involved in the same pathway.

In some cases, scaffolding proteins may also help activate some of the relay
proteins.
Termination of the Signal



For a cell of a multicellular organism to remain capable of
responding to incoming signals, each molecular change in its
signaling pathways must last only a short time.

Signal concentration must rise and fall.

If a signaling pathway component becomes locked into one state,
consequences can be dire.
The ability of a cell to receive new signals depends on the
reversibility of the changes produced by prior signals.

The cellular response only occurs when the concentration of
receptors with bound signaling molecules is above a certain
threshold.

When the number of active receptors falls below that threshold, the
cellular response ceases.
Relay molecules return to inactive form:

The GTPase activity intrinsic to a G protein hydrolyzes its bound
GTP.

Phosphodiesterase converts cAMP to AMP.

Phophatases inactivate phosphorylated kinases and other proteins.