B3L4 Modification of Protein Fxns

T/F: There is a limit to phosphorylation.

True

What three proteins often get phosphorylated?

1. Serine

2. Theronine

3. Tyrosine

When phosphate is added to a protein, what charge does it add?

-2 charge

• Proteins usually sit at a +1 charge, so adding a phosphate would make it -1

What are the four types of cellular receptors covered in class?

1. Ligand-gated ion channels

2. G-protein-coupled receptors

3. Catalytic receptors

4. Nuclear receptors

Ligand-gated ion channels

• Modify ion flux across the channel

• The channel can be a part of the receptor itself

Can ions act as a second messenger?

ONLY Ca²⁺ can act as a second messenger, Na⁺ and K⁺ cannot.

What are two examples of a ligand-gated ion channel?

1. Nicotinic ACh receptor - allows muscles to respond to neural signaling

2. ATP-sensitive K+ channels - located on β-cells to help with insulin secretion

GPCRs

• large classes of membrane proteins that activate second messengers

• Activate heterotrimeric α-proteins

What are the initial second messengers of GPCRs?

The products of enzymatic activity are the initial second messengers

What are heterotrimeric G-proteins?

This is your α-protein, β-protein, and γ-protein subunits on a GPCR

What is the ultimate purpose of GPCR?

Nucleotide exchange (to EXCHANGE GDP → for GTP on the α-subunit)

What is the difference between the on-state and the off-state in GPCRs?

Off state → high energy, high order

On state → low energy, low order

Catalytic Receptors

Enzymatic activity activation either a) within itself or b) initiated on another enzymatic complex

How are the initial second messengers activated in catalytic receptors?

Activated by enzymatic activity

Nuclear Receptors

Located in the cytoplasm or nucleus (hydrophobic)

• Act as transcription factors when bound to a ligand → modulates transcription of certain genes

Describe the steps of signaling events

1. Recognition (ligand binds to exofacial aspect of the receptor)

2. Transduction/Activation (ligand binding → conformational change → activates second messengers)

3. Transmission (2nd messenger activates w/ intracellular effectors)

4. Modulation of Effectors (activates kinases/phosphatases to interact with downstream targets)

5. Response (^ modifies cellular functions)

6. Termination (Feedback mechanisms stop signaling events and return fxns to basal state)

T/F: Amplification increases the amnt of reactions occuring/kinases activated

true

What would happen if K⁺ channels were suddenly unable to release?

The cell will depolarize → This is how β-cells release insulin

What are RGS molecules?

Molecules that promote GDP hydrolysis because without it, the process would be too slow