Chapter 16: Cell signaling

What is signal transduction?

A process where one type of signal is able to be converted into another signal

What are the 4 signaling methods animals cells use to communicate with another?

• Endocrine signaling

• Paracrine signaling

• Neuronal signaling

• Contact-dependent signaling

What is Endocrine signaling?

A type of long-distance-cell communication where endocrine glands secrete hormones and release them into the bloodstream, distributing them widely throughout the body

What is paracrine signaling?

A type of cell-to-cell communication where a cell releases paracrine signals into the extracellular space that diffuse a short distance to local neighboring cells

What is neuronal signaling?

A type of communication where a neuron transmits an electrical signal into its nerve terminal and triggers the release of neurotransmitters onto an adjacent target cell

What is contact dependent signaling?

A type of cell communication where the signal molecule of one cell binds to the receptor on an adjacent cell

What are cell surface receptors?

A type of protein that helps large hydrophilic signal molecules relay their message across the plasma membrane

What are intracellular receptors?

A type of protein present in the cytosol or nucleus that allows small or hydrophobic signal molecules to regulate gene transcription or other functions

Why can the same signal molecule induce different responses in different target cells?

Because each cell has their own unique receptors and internal signaling pathways that are different from one another

How do signal molecules regulate the behavior of an animal cell?

By working in combination to control whether a cell survives, differentiates, or divides.

What if a cell were to be deprived of any necessary survival signals?

The cell would undergo a form of cell suicide

Why do some cell responses to extracellular signals occur rapidly?

Due to the signal affecting the activity of proteins that are already present inside the target cell

Why do some cell responses to extracellular signals take minutes or hours to execute?

Due to the response to the extracellular signal requiring changes in gene expression and new proteins to be produced

How does an extracellular signal change the behavior of a target cell?

It binds to its cell-surface receptor and activating the intracellular signaling pathways, relaying its message through signaling molecules and eventually reaching the effector proteins that alter the cell’s behavior

What are the five things intracellular signaling proteins are able to do?

They are able to:

• Relay signals onward and help spread the signal throughout the cell with the help of scaffold proteins

• Amplify signals received and make them stronger,

• Detect signals from other intracellular pathways and integrate them into their own pathway

• Distribute signals to more than one effector protein

• And engage in feedback by modulating the response to a signal

What is positive feedback?

A self-perpetuating mechanism where a stimulus causes a response that amplifies the original stimulus, pushing a process to completion

What is negative feedback?

A self-regulating mechanism that reduces a change in a system to maintain stability

How does phosphorylation act as a molecular switch?

It acts as a molecular switch by turning a signaling protein on when a protein kinase adds a phosphate group to the protein, and turning it off when a protein phosphatase removes the phosphate group from the protein

What are the 3 classes of cell surface receptor?

• Ion-channel coupled receptors

• GPCR

• Enzyme coupled receptors

What are ion channel coupled receptors?

Receptors that can change the permeability of the P.M to specific ions and alter the membrane potential, and if the conditions are right, can also generate an electrical current

How do ion channel coupled receptors function?

When a signal molecule binds to the receptor, the channel undergoes conformational changing, resulting in the channel becoming open and allowing ions to pass through the membrane

What is GPCR?

A signaling mechanism that allows signals from the outside to enter the cell by the means of a G-protein

1. What is the general structure of a G protein?

2. How does the complex respond when activated by a GPCR?

3. How does the GTPase activity of G⍺ regulate its activation?

1. Its structure consist of 3 subunits: an alpha subunit and beta-gamma subunit

2. When a GPCR actiavtes the protein, a GTP molecule binds to the alpha subunit and causes the a-subunit to dissociates from the beta-gamma subunit

3. The GTPase activity of the a-subunit regulates its activation by hydrolyzing GTP into GDP, causing the subunits to recombine with each other and form the inactive G protein

How does a signal molecule activate a G protein inside the cell?

1. When a signal molecule binds to a GPCR, the receptor undergoes conformational change, resulting in GPCR becoming active

2. GPCR then interacts with its G protein and causes the a-subunit of the protein to release its GDP and exchange it with GTP

3. Resulting in the a-subunit and By-subunit dissociating from each other, allowing for both parts to interact with different target membrane proteins

How does the a-subunit of a G protein turn themselves off?

After the a-subunit activates a target enzyme or ion channel

1. The a-subunit hydrolyzes its GTP into GDP and becomes inactive

2. Resulting in the a-subunit reassociating with its By-subunit and reforming the inactive G protein for the next activation cycle

How do G proteins open K ion channels? what about closing them?

After the a-subunit binds to a GTP and dissociates from its B-complex:

1. The By complex then binds to and opens the K+ channel in the membrane and allows for K ions to flow out of the cell,

2. Resulting in the membrane becoming harder to activate and slowing the heart rate

 And to close the K ion channel

1. A-subunit hydrolyzes its GTP into GDP and becomes inactive, causing it to reassociate with the By subunit, resulting in the K channel closing

What are enzyme coupled receptors?

Receptors that either act as enzymes or associate with enzymes to send signals into the cell

How do enzyme coupled receptors function?

When a signal binds to the receptor, enzyme activity is switched on at the other end of the receptor inside the cell, triggering a wide variety of intracellular signaling pathways to occur

What increases when G proteins activate enzymes?

The concentration of secondary messengers increases

What are second messenger molecules able to do?

They’re able to bind to specific signaling proteins and influence their activity

How are cAMP molecules synthesized? How are they degraded?

cAMP molecules are synthesized by adenylyl cyclase removing 2 phosphate groups from an ATP molecule and binding the ribose sugar to the remaining phosphate group

cAMP molecules are degraded by cAMP phosphodiesterase breaking the bonds in the molecule, forming AMP

How does epinephrine cause a decrease in glycogen levels?

When the hormone activates GPCR and causes its G protein to activate adenylyl cyclase to boost the production of cAMP

1. cAMP molecules activate PKA, which triggers the phosphorylation and activation of phosphorylase kinase

2. Phosphorylase kinase then activates glycogen phosphorylase, the enzyme responsible for the break down of glycogen, and deactivates glycogen synthase, the enzyme responsible for producing glycogen,

Resulting in a decrease in glycogen in skeletal muscle cells

How does cAMP activate gene transcription?

When a cAMP molecule activates a PKA molecule, the PKA will enter the nucleus and phosphorylate specific transcription regulators, resulting in the regulators stimulating the transcription of a whole set of target genes

How do Calmodulin proteins have their structure changed?

By Ca molecules binding to their Ca binding sites that are on both ends of their structure

What are receptor-tyrosine-kinase (RTK)?

They are a type of enzyme-coupled receptor that has the ability to stimulate the assembly of an intracellular complex

How are RTKs activated?

1. When a signal molecule, in the form of a dimer, binds to the receptors present in the extracellular space, the receptors become dimerized

2. the formation of the dimer then allows for the receptors kinase domains to become close enough and activate each other, leading to the phosphorylation of several tyrosines on the cytosolic tails

3. After phosphorylation, RTK becomes activated with their phosphorylated tyrosines serving as a docking site for various intracellular signaling proteins, allowing signals to be transmitted into the cell’s interior

What are adaptor proteins able to recognize on an activated RTK tail?

They are able to recognize the phosphorylated tyrosines on the tail and bind to them, resulting in the assembly of complex cross linked, 3D signaling networks

How do RTKs activate a Ras protein?

1. When an adaptor protein docks onto an RTKs phosphorylated tyrosine, Ras-GEF is recruited and stimulates the Ras protein into exchanging its GDP for GTP

2. Resulting in the Ras protein becoming active and stimulating several downstream signaling pathways

How does RTK activate the MAP kinase signaling module?

After RTK converts Ras-GDP into Ras-GTP

1. Ras-GTP activates MAP kinase and passes it signal through the module, with each MAP kinase phosphorylating the next kinase as the signal moves down the module

2. With the final kinase phosphorylating various downstream targets such as effector proteins and/or signaling proteins

How does RTK activate the PI-3-kinase-Akt signaling pathway?

1. When a survival signal activates an RTK, Pi 3-kinase is recruited and activated

2. PI-3 kinase then phosphorylates an inositol phospholipid, resulting in a phosphorylated inosito phospholipid

3. Afterwards, the molecule attracts Akt where its then activated by Protein kinase 1 and 2

4. Once activated, Akt is released from the P.M to phosphorylate various downstream signaling pathways and proteins

How does the activation of Akt promote cell survival?

The activation of Akt causes the phosphorylation of BAD, triggering its inactivation and dissociation from Bcl2, blocking apoptosis from occurring and promoting cell survival as a result

How does Akt stimulate cell growth?

1. When a growth factor binds to an RTK and activates it, the activation of the PI-3-kinase-Akt signaling pathway is triggered as well

2. Akt then indirectly activates Tor by phosphorylating and inhibiting the protein essential in shutting tor down

3. Afterwards, Tor stimulates protein synthesis and inhibits protein degradation by phosphorylating key proteins in degradation, allowing for the cell to grow in size

What do GPCRs and RTKs have the ability to do?

They have the ability to activate multiple intracellular signaling pathways, with each pathway differing from another but still sharing common components to transmit their signals