The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals Cells can respond to many signals if they have a specific receptor for that signal. A signal transduction pathway is a sequence of molecular events and chemical reactions that lead to a cellular response, following the receptor’s activation by a signal.

Cells are exposed to many signals and may have different responses: Autocrine signals affect the same cells that release them. Paracrine signals diffuse to and affect nearby cells. Hormones travel to distant cells.

Only cells with the necessary receptors can respond to a signal—the target cell must be able to sense it and respond to it. A signal transduction pathway involves a signal, a receptor, and a response.

A common mechanism of signal transduction is allosteric regulation. This involves an alteration in a protein’s shape as a result of a molecule binding to it. A signal transduction pathway may produce short or long term responses. A signal molecule, or ligand, fits into a three- dimensional site on the receptor protein. Binding of the ligand causes the receptor to change its three-dimensional shape. The change in shape initiates a cellular response.

Ligands are generally not metabolized further, but their binding may expose an active site on the receptor. Binding is reversible and the ligand can be released, to end stimulation. An inhibitor, or antagonist, can bind in place of the normal ligand.

Transduction

Receptors can be classified by their location in the cell. This is determined by whether or not their ligand can diffuse through the membrane. Cytoplasmic receptors have ligands, such as estrogen, that are small or nonpolar and can diffuse across the membrane. Membrane receptors have large or polar ligands, such as insulin, that cannot diffuse and must bind to a transmembrane receptor at an extracellular site.

Receptors are also classified by their activity: Ion channel receptors, or gated ion channels, change their three-dimensional shape when a ligand binds.

Protein kinase receptors change their shape when a ligand binds. The new shape exposes or activates a cytoplasmic domain that has catalytic (protein kinase) activity.

Protein kinases catalyze the following reaction: ATP + protein  ADP + phosphorylated protein Each protein kinase has a specific target protein, whose activity is changed when it is phosphorylated.

Ligands binding to G protein–linked receptors expose a site that can bind to a membrane protein, a G protein. The G protein is partially inserted in the lipid bilayer, and partially exposed on the cytoplasmic surface.

Signal activation of a specific receptor leads to a cellular response, which is mediated by a signal transduction pathway. Signaling can initiate a cascade of protein interactions—the signal can then be amplified and distributed to cause different responses. A second messenger is an intermediary between the receptor and the cascade of responses. In the fight-or-flight response, epinephrine (adrenaline) activates the liver enzyme glycogen phosphorylase. The enzyme catalyzes the breakdown of glycogen to provide quick energy.

Researchers found that the cytoplasmic enzyme could be activated by the membrane-bound epinephrine in broken cells, as long as all parts were present. They discovered that another molecule delivered the message from the “first messenger,” epinephrine, to the enzyme. The second messenger was later discovered to be cyclic AMP (cAMP). Second messengers allow the cell to respond to a single membrane event with many events inside the cell—they distribute the signal. They amplify the signal by activating more than one enzyme target.

Signal transduction pathways involve multiple steps—enzymes may be either activated or inhibited by other enzymes. In liver cells, a signal cascade begins when epinephrine stimulates a G protein–mediated protein kinase pathway. Epinephrine binds to its receptor and activates a G protein. cAMP is produced and activates protein kinase A—it phosphorylates two other enzymes, with opposite effects:

Inhibition—protein kinase A inactivates glycogen synthase through phosphorylation, and prevents glucose storage. Activation—Phosphorylase kinase is activated when phosphorylated and is part of a cascade that results in the liberation of glucose molecules.

Figure 5.17 A Cascade of Reactions Leads to Altered Enzyme Activity (Part 1 )

Figure 5.17 A Cascade of Reactions Leads to Altered Enzyme Activity (Part 2)

Signal transduction ends after the cell responds— enzymes convert each transducer back to its inactive precursor. The balance between the regulating enzymes and the signal enzymes determines the cell’s response.

Cells can alter the balance of enzymes in two ways: Synthesis or breakdown of the enzyme Activation or inhibition of the enzymes by other molecules Cell functions change in response to environmental signals: Opening of ion channels Alterations in gene expression Alteration of enzyme activities

Question #2: 1999 Communication occurs among the cells in a multicellular organism. Choose THREE of the following examples of cell-to-cell communication, and for each example, describe the communication that occurs and the types of responses that result from this communication. Communication between two plant cells Communication between two immune system cells Communication either between a neuron and another neuron, or between a neuron and a muscle cell Communication between a specific endocrine-gland cell and its target cell