In multicellular organisms Cell communication In multicellular organisms

3 stages of cell signaling 1. reception – (p. 209) A chemical signal is detected when a signaling molecule binds to a receptor protein on the cell surface or inside the cell. 2. transduction – (210) converts the signal to a form that can bring about a response; often requires a series of changes- a signal transduction pathway. 3. response – (210) may be almost any cellular activity, in response to the transduction pathway.

Types of reception (211-213) G Protein-Coupled receptor: widespread and diverse in their function. When the receptor is activated by the appropriate signaling molecule, the receptor changes shape and binds to an inactive G protein, activating it. The G protein then diffused along the membrane an binds to an enzyme, altering its shape and activity. Next, the enzyme can trigger the next step leading to a cellular response.

Types of reception (211-213) 2. Receptor Tyrosine Kinases: attach phosphates to tyrosines Many exists as individual units until the binding of a signaling molecule causes two receptor monomers to form a “dimer”. Dimerization activates the tyrosine region, adding a phosphate from an ATP molecule. Once activated, it is recognized by relay proteins inside the cell. After binding, a transduction pathway is activated, leading to a cellular response.

Types of reception (211-213) Ligand-gated ion channel: signaling molecule (ligand) binds to a receptor protein. The “gate” opens or closes, allowing or blocking the flow of specific ions. EX- neurotransmitters in the nervous system

What are the similarities among the following? G protein-coupled receptors receptor tyrosine kinases ion channel receptors

Transduction (214-218) a multistep pathway - a chain of molecular interactions – the signal conducting pathway – at each step, the signal is transduced into a different form, usually a shape change in a protein brought about by adding or taking of a phosphate group. (*phosphorylation cascade)

Phosphorylation Cascade An enzyme that transfers phosphate groups from ATP to a protein is generally known as a protein kinase. Equally important in the phosphorylation cascade are the protein phosphatases –enzymes that can rapidly remove phosphate groups from proteins (dephosphorylation). Phosphatases also make protein kinases available for reuse, enabling the cell to respond again to an extracellular signal.

Phosphorylation In reactions mediated by protein kinases, what does phosphorylation of successive proteins do to drive the reaction? make functional ATP change a protein from its inactive to its active form change a protein from its active to its inactive form alter the permeability of the cell’s membranes produce an increase in the cell’s store of inorganic phosphates Answer: b Note: some responses would be true if the question were not specifically about driving a reaction.

Phosphorylation In reactions mediated by protein kinases, what does phosphorylation of successive proteins do to drive the reaction? make functional ATP change a protein from its inactive to its active form change a protein from its active to its inactive form alter the permeability of the cell’s membranes produce an increase in the cell’s store of inorganic phosphates Answer: b Note: some responses would be true if the question were not specifically about driving a reaction.

Small molecules & ions as Second Messengers Many signaling pathways also involve small, non-protein, water soluble molecules or ions called second messengers. Because second messengers are small and water-soluble, they can readily spread throughout the cell by diffusion. The two most widely used second messengers are cyclic AMP and Ca+. A wide variety of relay proteins are sensitive to cytosolic concentrations of one or the other of these.

Signal Transduction Which of the following best describes a signal transduction pathway? binding of a signal molecule to a cell protein catalysis mediated by an enzyme sequence of changes in a series of molecules resulting in a response binding of a ligand on one side of a membrane that results in a change on the other side the cell’s detection of a chemical or mechanical stimulus Answer: c

Signal Transduction Which of the following best describes a signal transduction pathway? binding of a signal molecule to a cell protein catalysis mediated by an enzyme sequence of changes in a series of molecules resulting in a response binding of a ligand on one side of a membrane that results in a change on the other side the cell’s detection of a chemical or mechanical stimulus Answer: c

Response 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

Nuclear and Cytoplasmic Responses 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 © 2011 Pearson Education, Inc.

Nuclear and Cytoplasmic Responses Other pathways regulate the activity of enzymes rather than their synthesis. EX- The hormone epinephrine acts to activate a succession of relay molecules. The final protein (the enzyme glycogen phosphorylase) acts to release glucose monomers from glycogen.

Response Signaling pathways can also affect the overall behavior of a cell, for example, changes in cell shape. EX – mating behavior in yeast.

Apoptosis Apoptosis is programmed or controlled cell suicide. Components of the cell are chopped up and packaged into vesicles that are digested by scavenger cells Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells

Apoptosis One of the important outcomes of apoptosis is protection of neighboring cells. Which of the following is responsible? cell shrinkage and blebbing destruction of the cell’s DNA formation of numerous vesicles to be digested action of tyrosine kinases activation of specific proteins Answer: c

Apoptosis One of the important outcomes of apoptosis is protection of neighboring cells. Which of the following is responsible? cell shrinkage and blebbing destruction of the cell’s DNA formation of numerous vesicles to be digested action of tyrosine kinases activation of specific proteins Answer: c

Cancer and Apoptosis How could cancer result from a defect in apoptosis?

Apoptosis Apoptosis is important in shaping an organism during embryonic development Apoptosis can be triggered by An extracellular death-signaling ligand DNA damage in the nucleus Protein misfolding in the endoplasmic reticulum

Signal Overview Indicate where each of the labels should appear in the figure. Receptor molecule Relay molecules Transduction Activation of cellular response Signaling molecule Response Reception

Signal Amplification Which of the following is an example of signal amplification? catalysis of many cAMP molecules by several simultaneously binding signal molecules activation of 100 molecules by a single signal binding event activation of a specific gene by a growth factor activation of an enzyme molecule utilization of a second messenger system Answer: b

Signal Amplification Which of the following is an example of signal amplification? catalysis of many cAMP molecules by several simultaneously binding signal molecules activation of 100 molecules by a single signal binding event activation of a specific gene by a growth factor activation of an enzyme molecule utilization of a second messenger system Answer: b