Bio 121 Unit 3: Cell Communication

Receptor Tyrosine Kinases

Category of enzyme-linked receptors found in animals; Recognize various types of signaling molecules; Example: Epidermal Growth Factor (EGF). One function is to stimulate epidermal cells to divide. Functions in many different contexts;

Q1: The process through which cells can detect and respond to signals in their extracellular environment is _____.

Cell communication

Signals relayed between cells: Direct intercellular signaling

Cell junctions allow signaling molecules to pass from one cell to another;

Apoptosis: programmed cell death

Cell shrinks and forms rounder shape due to destruction of nucleus and cytoskeleton;

Q13: What do synaptic signaling and paracrine signaling have in common?

Cells release a signal that affects neighboring cells.

Signals relayed between cells: Autocrine signaling

Cells secrete signaling molecules that bind to their own cell surface or similar neighboring cells;

Q17: A key is placed into a keyhole then turned and the door opens. When considering the components of cell signaling, the action of turning the key would best correspond to

Conformational change in the receptor once bound to the hormone

Jealousy comes from counting other people's blessings instead of your own...

Count your blessings!

cAMP

Cyclic adenosine monophosphate (cAMP, cyclic AMP or 3'-5'-cyclic adenosine monophosphate) is a second messenger important in many biological processes. cAMP is derived from adenosine triphosphate (ATP) and used for intracellular signal transduction in many different organisms, conveying the cAMP-dependent pathway.

Cellular response

Different responses possible Change enzyme activity Change function of structural proteins Change gene expression;

Q10: When sodium ions move from one cardiac muscle cell to an adjacent cell causing them to contract in unison this is an example of ____.

Direct intercellular signaling

Kd

Dissociation Constant between a ligand and its receptor. The Kd value is inversely proportional to the affinity between the ligand and its receptor. A low Kd value indicates that a receptor has a high affinity for its ligand.

This explains effect of caffeine

1. Caffeine inhibits phosphodiesterase, the enzyme that removes cAMP once the signal is gone 2. Inhibition causes cAMP to persist, so heart beats faster even with low epinephrine;

3 Types of Cell surface receptors

1. Enzyme-linked receptors 2. G-protein coupled receptors (GPCR) 3. Ligand-gated ion channels

G-protein coupled receptors (GPCR)

1. Found in all eukaryotes, common in animals 2. 7 transmembrane segments 3. Activated receptor binds to G protein 4. Releases GDP and binds GTP instead 5. GTP causes G protein to dissociate α subunit and β/γ dimer interact with other proteins in a signaling pathway;

Enzyme-linked receptors

1. Found in all living species; 2. Extracellular domain binds signal; 3. Intracellular domain becomes functional catalyst; 4. Most are protein kinases;

Ligand-gated ion channels

1. Plant and animal cells; 2. Ligand binding causes ion channels to open and ions to flow through the membrane; 3. In animals, these transmit synaptic signals between neurons and muscles or between two neurons;

3 stages of cell signaling

1. Receptor activation; 2. Signal transduction; 3. Cellular response;

cAMP has 2 advantages!

1. Signal amplification: Binding of signal to one receptor can cause the synthesis of many cAMP molecules that activate PKA, and each PKA can phosphorylate many proteins; 2. Speed: In one experiment a substantial amount of cAMP was made within 20 seconds after addition of signal;

Ligand

1. Signaling molecule; 2. Binds noncovalently to receptor with high specificity; 3. Binding and release between receptor and ligand relatively rapid; 4. Ligand binding changes receptor structure - this conformational change transmits the signal across the membrane; 5. Once a ligand is released, the receptor reverts andis inactive again;

Q22: A G-protein coupled receptor associates with a G protein that contains how many subunits?

3

Signal transduction

Activated receptor stimulates a sequence of changes - a signal transduction pathway;

What do signals in extracellular environment regulate?

Activities in multicellular organism. By changing the conformation of a receptor, signals lead to a response inside the cell;

Differential gene expression

All cells contain the same genome but only express particular genes;

Q34: The production of second messengers in signal transduction offers at least two advantages, speed and

Amplification.

Q37: Some anti-cancer drugs block signal transduction pathways activated by growth factors. Which of the following would be a good target for such a drug?

An inhibitor of a protein kinase cascade.

Q5: During exposure to elevated glucose, a yeast cell will increase its uptake of glucose. Describe the mechanism by which the yeast sense the extracellular glucose.

By glucose binding to glucose receptors;

Q15: When the concentration of a ligand is equal to the KD which of the following is true?

Half of the receptors are bound to ligands.

Q11: Diabetics can be given the ____ insulin which binds to receptors on cells throughout the body increasing glucose uptake.

Hormone

Q28: When receptors coupled to phospholipase C are activated, calcium levels in the cytosol increase when ______

IP3 binds to ligand-gated channels on the endoplasmic reticulum, releasing calcium

What happens when Kd = [Ligand]?

Ligand concentration at which half of the receptors have bound ligand;

Q35: IP3 binds to _____ receptors.

Ligand-gated Ca2+ channel

Q23: When a neurotransmitter released from one neuron binds to a ______ on a second neuron, that neuron depolarizes and fires.

Ligand-gated ion channel

Signals relayed between cells: Contact-dependent signaling;

Molecules bound to the surface of cells serve as signals to cells coming in contact with them;

Q18: If the concentration of a ligand is 100 times greater than the Kd of its receptor, _______ of the receptors will be bound to a ligand.

Most

Apoptosis

Process of cell death, which occurs naturally as part of normal development, maintenance, and renewal of tissues within an organism.

Cell Communication

Process of cells detecting and responding to signals in the extracellular environment;

Q3: A substrate binding to an enzyme is most similar to a signal molecule binding to a

Receptor

Signals relayed between cells: Paracrine signaling

Signal does not affect originating cell, but does influence nearby cells;

Receptor activation

Signaling molecule binds to receptor

G-protein-coupled receptors

Signals binding to cell surface are "first messenger";

Signals relayed between cells: Endocrine signaling

Signals called hormones travel long distances and are usually longer lasting in effect;

Intracellular receptors

Some receptors are inside the cell! Example: Estrogen Hormone passes through cell membrane and into the nucleus where it binds estrogen receptor The estrogen•receptor complex binds DNA and regulates gene transcription

Q20: When insulin binds to it's G-protein coupled receptor (GPCR) what happens next?

The G protein loses GDP and gains GTP becoming activated.

Q21: Following its initial activation, how does a G protein become inactivated?

The G-protein a subunit GTP is hydrolyzed to GDP allowing reassociation of the G-protein a subunit and bg dimer.

Phototropism

The growth of plant organs in response to light. Aerial shoots usually grow towards light, while some aerial roots grow away from light. The phototropic response is thought to be controlled by auxin, a plant growth substance;

Q24: Estrogen is a lipid soluble hormone that can easily cross membranes. Knowing this, what can be concluded about estrogen receptors?

The receptors would be found inside the cell.

Hormonal Signaling in Multicellular Organisms

The response to a given signaling molecule depends on which cell is responding; The variation in response is determined by the set of proteins that each cell makes (the proteome);

Auxin

The signaling molecule responsible for phototropism; It is: inhibited by light and transmitted from cell to cell;

Q42: Patients who have type 2 diabetes no longer respond normally to insulin. This symptom would be best explained by

Their cells express less insulin receptor.

Q16: What do G-protein coupled, enzyme-linked, and ligand-gated ion channel receptors have in common?

They change their conformation when bound to a hormone.

Q41: If you add the plant hormone auxin to one side of a plant the cells exposed to the auxin elongate. If you measured auxin levels in plant cells exposed to light what you would you expect to find?

They would be lower, causing the plant to bend towards the light

Why else do cells send signals?

To communicate with each other: cell-to-cell communication; Example: Phototropism in plants allows multiple cells to change shape, bending the plant in a coordinated way;

Why do cells send signals?

To respond to changing environment. These signals can be critical for survival. Example: Glucose signals yeast cells to increase glucose transporters and enzymes allowing efficient uptake and use of glucose;

Q29: After estrogen binds to receptors, these estrogen receptors gain ______ activity.

Transcription factor

Q43: Patients who have type 2 diabetes no longer express genes when exposed to insulin. How might this phenomenon be explained?

Transcription factors normally activated by insulin remain off

Q26: A phosphatase is capable of dephosphorylating molecules. What would this enzyme do in a signal transduction pathway that used a kinase cascade?

Turn off the cascade

Q39: Smooth muscle cells in the airways relax while those in the blood vessels contract in response to the hormone epinephrine. What would you expect to be different in these two types of cells exposed to epinephrine?

Types of proteins expressed.

What produces the cellular response to signals?

Typically, the signaling molecule binds to cell surface receptor and the conformation change stimulates a signal transduction pathway; Signal transduction pathways may involve a cascade of intracellular kinases, or generation of intracellular signals called second messengers

Q32: A hormone binds a receptor and activates the cAMP signal transduction pathway ultimately leading to the cell response. If you wanted to develop a drug to block this pathway the drug would need to inhibit _____

adenylyl cyclase

Q25: When epinephrine binds to its G-protein linked receptor ____ is activated producing ___.

adenylyl cyclase, cAMP

Q31: When cAMP is produced in a cell it will then ______.

bind to a repressor of protein kinase A

Q36: Phospholipase C hydrolyzes a membrane phospholipid to produce ____

both IP3 and diacylglycerol

Q2: In some cases, just a few hormone molecules binding to the surface of a cell can trigger a very large response because ____.

the signal is amplified by activation of enzymes that each catalyze multiple reactions

Q30: What do enzyme-linked receptors and growth factor receptors have in common?

Both possess kinase activity when bound to a hormone

Q40: Programmed cell death is known as ____. autophagy

Apoptosis

Q14: When a cell responds to a signal it sent this is an example of _____.

Autocrine signaling

Q8: When a cell secretes a growth factor that binds to receptors on its own membrane preventing it from proliferating this is an example of ____.

Autocrine signaling

Q12: Hormones are released from one cells and act on other cells in distant organs and are thus an example of ____.

Endocrine signaling

Q9: When insulin is secreted from the pancreas and acts on muscle cells to increase glucose uptake this is an example of ____.

Endocrine signaling

Q19: When epidermal growth factor binds to its _____________ the receptor phosphorylates itself, triggering a signal transduction pathway.

Enzyme-linked receptor

Example of hormonal signaling

Epinephrine: Fight-or-flight hormone Has different effects throughout the body: 1. Airways of the lungs relax to provide more oxygen 2. More glycogen breakdown in skeletal muscle 3. Heart muscle cells beat faster

Q4: After being fed glucose a cell increases its intracellular glucose concentrations by _____ .

Increasing membrane glucose transporters;

Q38: Epinephrine blocks the contraction of muscles in the airways. Which of the other activities of epinephrine is most likely to be regulated by the same type of pathway?

Inhibition of saliva production in salivary glands

A Cell's Response to Hormones and Other Signaling Molecules Depends on the Proteins It Makes

One hormone causes different effects in different cell types;

Q6: When a cell secretes a growth factor that binds to receptors on neighboring cells causing them to proliferate this is an example of ____.

Paracrine signaling

Q7: When a cell secretes a growth factor that binds to receptors on neighboring cells causing them to proliferate this is an example of _____.

Paracrine signaling

Q33: The molecule directly responsible for breaking down cAMP to inactive AMP is

Phosphodiesterase

Q27: Adenylyl cyclase is to cAMP as ________ is to IP3.

Phospholipase C; Adenylyl cyclase:cAMP = PLC:IP3

Blebs

Plasma membrane forms blebs - irregular extensions that break away;

If you are going through hell.....

keep going. Winston Churchill