Concept 11.4 Response: Cell signaling leads to regulation of transcription or cytoplasmic activities Flashcards
We now take a closer look at the cell’s subsequent response to an extracellular signal—what some researchers call the
“output response.”
The response at the end of the pathway may occur in the
nucleus of the cell or in the cytoplasm
Many signaling pathways ultimately regulate protein synthesis, usually by turning specific
genes on or off in the nucleus.
Like an activated steroid receptor (see Figure 11.9), the final activated molecule in a signaling pathway may function as a
transcription factor.
The response to this growth factor signal is transcription, the synthesis of one or more specific mRNAs, which will be translated in the
cytoplasm into specific proteins.
In other cases, the transcription factor might regulate a gene by
turning it off
Sometimes a signaling pathway may regulate the activity of proteins rather than causing their
synthesis by activating gene expression
This directly affects proteins that function outside the
nucleus
The final step in the signaling pathway that begins with epinephrine binding activates the
enzyme that catalyzes the breakdown of glycogen.
participate in a variety of pathways, leading to both nuclear and cytoplasmic responses, including cell division
Signal receptors, relay molecules, and second messengers
Malfunctioning of growth factor pathways like the one in Figure 11.15 can contribute to abnormal cell division and the development of
cancer
Whether the response occurs in the nucleus or in the cytoplasm, it is not simply turned ______________ Rather, the extent and specificity of the response are regulated in multiple ways.
“on” or “off.”
Here we’ll consider four aspects of this regulation. First, as mentioned earlier, signaling pathways generally
amplify the cell’s response to a single signaling event.
The degree of amplification depends on the
function of the specific molecules in the pathway
Second, the many steps in a multistep pathway provide control points at which the cell’s response can be further
regulated, contributing to the specificity of the response and allowing coordination with other signaling pathways.
Third, the overall efficiency of the response is enhanced by the presence of proteins known as
scaffolding proteins.
Finally, a crucial point in regulating the response is the
termination of the signal.
Elaborate enzyme cascades amplify the cell’s response to a
signal.
At each catalytic step in the cascade, the number of activated products can be
much greater than in the preceding step
For example, in the epinephrine-triggered pathway in Figure 11.16, each adenylyl cyclase molecule catalyzes the formation of 100 or so cAMP molecules, each molecule of protein kinase A phosphorylates about
10 molecules of the next kinase in the pathway, and so on.
The amplification effect stems from the fact that these proteins persist in their
active form long enough to process multiple molecules of substrate before they become inactive again.
As a result of the signal’s amplification, a small number of epinephrine molecules binding to receptors on the surface of a liver cell or muscle cell can lead to the
release of hundreds of millions of glucose molecules from glycogen.
Consider two different cells in your body—a liver cell and a heart muscle cell, for example. Both are in contact with your
bloodstream and are therefore constantly exposed to many different hormone molecules, as well as to local regulators secreted by nearby cells.
Yet the liver cell responds to some signals but ignores others, and the same is true for the
heart cell.
epinephrine stimulates the liver cell to break down glycogen, but the main response of the heart cell to epinephrine is
contraction, leading to a more rapid heartbeat.
The explanation for the specificity exhibited in cellular responses to signals is the same as the basic explanation for virtually all differences between cells: .
Because different kinds of cells turn on different sets of genes, different kinds of cells have different collections of proteins
The response of a cell to a signal depends on its particular collection of
signal receptor proteins, relay proteins, and proteins needed to carry out the response.
In many cases, the efficiency of signal transduction is apparently increased by the presence of
scaffolding proteins, large relay proteins to which several other relay proteins are simultaneously attached
Researchers have found scaffolding proteins in brain cells that permanently hold together
networks of signaling pathway proteins at synapses.
This hardwiring enhances the
speed and accuracy of signal transfer between cells because the rate of protein-protein interaction is not limited by diffusion.
The importance of the relay proteins that serve as points of branching or intersection in signaling pathways is highlighted by the problems arising when these proteins are
defective or missing.
in an inherited disorder called __________________________ , the absence of a single relay protein leads to such diverse effects as abnormal bleeding, eczema, and a predisposition to infections and leukemia.
Wiskott-Aldrich syndrome (WAS)
These symptoms are thought to arise primarily from the
absence of the protein in cells of the immune system.
By studying normal cells, scientists found that the WAS protein is located just beneath the
immune cell surface.
The protein interacts both with microfilaments of the cytoskeleton and with several different components of signaling pathways that relay information from the
cell surface, including pathways regulating immune cell proliferation.
This multifunctional relay protein is thus both a branch point and an important intersection point in a complex signal transduction network that controls
Immune cell behavior
When the WAS protein is absent, the cytoskeleton is not properly organized and signaling pathways are disrupted, leading to the
WAS symptoms.
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.
if a signaling pathway component becomes locked into one state, whether active or inactive, consequences for the organism
can be serious.
The ability of a cell to receive new signals depends on reversibility of the changes produced by
prior signals.
The binding of signaling molecules to receptors is
reversible.
As the external concentration of signaling molecules falls, fewer receptors are bound at any given moment, and the unbound receptors
revert to their inactive form.
The cellular response occurs only 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. Then, by a variety of means, the relay molecules return to their inactive forms: .
The GTPase activity intrinsic to a G protein hydrolyzes its bound GTP; the enzyme phosphodiesterase converts cAMP to AMP; protein phosphatases inactivate phosphorylated kinases and other proteins; and so forth. As a result, the cell is soon ready to respond to a fresh signal
