AP Biology

Ch. 11 Cell Signaling

Overview of Cell Signaling

• Cell signaling evolved early in the history of life. Evidence is that signaling in microbes has much in common with the process in multi-cellular organisms.

• The process by which a signal on a cell’s surface is converted into a specific cellular response is a series of steps called a signal-transduction pathway.

Cell Signaling, cont.

• Cells communicate with one another by means of chemical signals.

• The cell targeted by a particular signal has a receptor molecule complementary to the signal molecule, or ligand. The ligand fits like a key in a lock and triggers a change in the receptor molecule.

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Communication between mating yeast cells >

Communication between cells

• Communicating cells may be close together or far apart. Animal cells signal with nearby cells by secreting local regulators, or if nerve cells, neurotransmitters at synapses.

• Both animal and plant cells use hormones for signaling over long distances.

• Cells can also communicate by direct contact.

Cell Communication

Communication by direct contact

Q: Which of the following is true of intercellular junctions such as tight junctions, desmosomes, and gap junctions?

• A) They are specialized forms of communication among nerve cells.

• B) They are of primary importance in the contraction of skeletal muscle cells.

• C) They are equally distributed among all tissue types.• D) They help to integrate cells into a functioning unit.• E) They aid in distributing DNA among cells.

Q: Which of the following provides the best evidence that cell-signaling pathways evolved early in the history of life?

• A) They are seen in primitive cells such as yeast.• B) Signal transduction molecules found in distantly

related organisms are similar.• C) Signals can be sent long distance by cells.• D) Most signals have surface receptors.• E) Yeast signal each other for mating.

Stages of Cell Signaling

• The three stages of cell signaling are reception, transduction, and response.

• Earl Sutherland discovered how epinephrine binds to receptors on a cell’s surface (reception), leading to a series of changes in the receptor and other molecules inside the cell (transduction) and finally to the activation of an enzyme that breaks down glycogen (response).

Cell Signaling Overview

Signal Reception

• A signal molecule binds to a receptor protein, causing the protein to change shape.

• The binding between signal molecule (ligand) and receptor is highly specific.

• A conformational change in a receptor is often the initial transduction of the signal.

Signal molecules

• Hormones can be classified as polypeptides (proteins and peptides), amines, and steroids

• Binding of water-soluble hormones to cell-surface receptors triggers intracellular signal transduction, leading to specific responses in the cytoplasm or changes in gene expression. Ex) epinephrine

• Lipid-soluble hormones and intracellular receptors act in the nucleus to regulate transcription of genes. Ex) testosterone and estrogen

G-protein-linked receptors

• Most signal receptors are plasma membrane proteins.

• A G-linked receptor is a membrane receptor that works with the help of a cytoplasmic G protein.

• Ligand binding activates the receptor, which then activates a specific G-protein, which activates yet another protein in a signal-transduction pathway.

• Epinephrine uses this sort of receptor.

G-protein-linked receptor

Tyrosine-kinase receptors

• Tyrosine-kinase receptors react to the binding of signal molecules by forming dimers and then adding phosphate groups to tyrosines on the cytoplasmic side of the receptor.

• Relay proteins in the cell can then be activated by binding to different phosphorylated tyrosines, allowing this receptor to trigger several pathways at once.

• Growth factors commonly use tyrosine-kinase receptors.

Ion-channel receptors

• Specific signal molecules cause ligand-gated ion channels in a membrane to open or close, regulating the flow of specific ions, such as Na+ or Ca2+.

• Ligand-gated ion channels are very important in the nervous system, controlled by electrical signals.

Q: The activation of receptor tyrosine kinases is always characterized by

• A) dimerization and phosphorylation• B) IP3 binding• C) a phosphorylation cascade• D) GTP hydrolysis• E) channel protein conformational change

Q: Binding of a signal molecule to which type of receptor leads directly to a change in the distribution of anions and/or cations on opposite sides of the membrane?

• A) receptor tyrosine kinase• B) G-protein linked receptor• C) intracellular receptor• D) ligand-gated ion channel• E) phosphorylated kinase dimer

Intracellular receptors

• Intracellular receptors are cytosolic or nuclear proteins.

• Signal molecules that can readily cross the plasma membrane, such as steroid hormones and nitric oxide, use these receptors.

Steroid hormone interacts with intracellular receptors

• Testosterone passes through the plasma membrane.

• Testosterone binds to a receptor protein in the cytosol, activating it.

• The receptor-hormone complex enters the nucleus and binds to specific genes.

• The bound protein stimulates the transcription of the gene into mRNA.

• The mRNA is translated into a specific protein.

Signal-transduction pathways

• Pathways relay signals from receptors to cellular responses, usually by a multi-step pathway.

• At each step in a pathway, the signal is transduced into a different form, commonly a conformational change in a protein.

Protein phosphorylation

• Protein phosphorylation, a common mode of regulation in cells, is a major mechanism of signal transduction.

• Many signal-transduction pathways include phosphorylation cascades, in which a series of protein kinases successively add phosphate groups to the next one in line, activating it.

• Phosphatase enzymes soon remove the phosphates.

A phosphorylation cascade

Cyclic AMP

• Certain small molecules and ions are key components of signaling pathways as “second messengers”.

• Second messengers, such as cyclic AMP (cAMP) and Ca2+, diffuse readily through the cytosol and help broadcast signals quickly.

• Many G proteins activate adenylyl cyclase, which makes cAMP from ATP.

Cyclic AMP: Second messengers

Q: Phosphorylation cascades involving a series of protein kinases are useful for cellular signal transduction because

• A) they are species specific.• B) they always lead to the same cellular response.• C) they amplify the original signal manyfold.• D) they reverse the effects of phosphatases.• E) the number of molecules involved is small and fixed.

Calcium Ions and IP3• Ca2+ can serve as a messenger because protein pumps

usually keep it at lower concentrations in the cytosol than outside the cell.

• IP3 (inositol triphosphate) is the ligand for a gated calcium channel in the membrane of the ER, which stores Ca2+ at high concentrations.

• When IP3 binds, Ca2+ flows into the cytosol, where it activates proteins of many signaling pathways.

• Increasing cytosolic concentration of Ca2+ causes many responses in animal cells, including muscle contraction, secretion of certain substances, and cell division. In plant cells, it is involved in adaptive responses to environmental stresses, such as drought or cold.

Calcium and IP3 in signaling pathways

Cellular Responses to Signals

• In response to a signal, a cell may regulate activities in the cytoplasm or transcription in the nucleus.

• For example, signaling pathways regulate enzyme activity and cytoskeleton rearrangement in the cytoplasm.

• Other pathways regulate genes; they do this by activating transcription factors, proteins that turn specific genes on or off.

Signal Amplification

• Elaborate pathways amplify and specify the cell’s response to signals.

• Each catalytic protein in a signaling pathway amplifies the signal by activating multiple copies of the next component of the pathway.

• Scaffolding proteins can increase signal-transduction efficiency by holding components of a pathway together.

Cytoplasmic response to a signal: The stimulation of glycogen breakdown

by epinephrine

Refer to the molecules on the left for #1-4

• A) Adenylyl cyclase• B) G-protein• C) Carrier protein• D) cAMP• E) Ion channel

receptor protein

• 1) Activated by directly binding to GTP

• 2) Catalyzes the formation of cytosolic second-messenger molecules

• 3) Enhances the transport of lipophilic signals in the blood

• 4) Serves as an intracellular second messenger

Q: Which of the following is typically NOT a component of a signal transduction pathway?

• A) production of more signal• B) production of second messengers such as cAMP• C) expression of specific proteins• D) activation of protein kinases• E) phosphorylation of certain transcription factors

Q: Lipid-soluble signal molecules, such as testosterone, cross the membranes of all cells but affect only target cells because

• A) only target cells have the appropriate DNA segments.• B) intracellular receptors are present only in target cells.• C) most cells lack surface receptors to inhibit lipid

soluble molecules.• D) only target cells produce testosterone.• E) most cells lack the enzymes to utilize testosterone.