Signal Transduction

Question 1

1. Provide examples of four types of signaling systems in the body

Answer 1

● Contact dependent - immune cells must contact
○ Example → immune cells

● Paracrine- wound healing cell signals close by
○ Example 1→ regulate inflammation at infection site.

● Synaptic- neurotransmitters transmit via synapse
○ Example → neurotransmitters

● Endocrine- hormone cells signal to other cells far away
○ example→ hormones

Question 2

2. Describe the changes that occur in some proteins (modifications, nucleotide binding, conformational changes) that allow them to act as molecular switches.

Answer 2

a. Proteins act as molecular switches that converting them from an inactive (non-signaling) form to an active (signaling)
i. upstream signal induces change to enable downstream signaling

Question 3

3. Be able to sketch a generic signal transduction pathway that includes a receptor, intracellular signaling proteins, and effector proteins.

Answer 3

see sheet for pathway:

Question 4

4. Describe the molecular aspects of signaling complexes and common interaction domains, and how they provide speed and specificity in signal transduction.

Answer 4

a. Types of Receptors
i. Ligand-gated ion channels
1. Milliseconds
2. Ex: nicotinic ACh receptor

ii. Enzyme-coupled receptor
1. Receptor Tyrosine Kinase & SER/THR Kinases
2. Seconds to minutes
3. Ex: insulin receptor

iii. GPCRs - G Protein Coupled Receptors
1. Seconds to minutes
2. Ex: beta-adrenergic receptor

b. Interaction Domains
i. SH2 → SRC Homology 2: binds phosphotyrosine
ii. SH3 → SRC Homology 3: binds protein rich domains
iii. PTB → phosphotyrosine binding
iv. PH → Pleckstrin homology; binds phosphatidylinositol

Question 5

5. Recognize the types of molecular signals (steroid) that are ligands of nuclear receptors.

Answer 5

● Nuclear receptors are ligand modulated proteins

● Respond to steroid hormones: cholesterol
○ Cholesterol is a major component of cell membranes,

○ hydrophobic and need carrier proteins to transport.

○ Small hydrophobic hormones can cross the membrane and then interact w/ intracellular receptors.

● respond to intracellular signals - peroxisome.

Question 6

6. Describe how nuclear receptor modulator drugs can be effective even as partial agonists.

Answer 6

Estrogen Receptors
● Estradiol - recognizes the estrogen receptor.
- associated w/ inhibitory proteins till ligand binding allows estrogen to bind with DNA.

● Cofactors - needed to initiate gene expression

● by decreasing activity of estrogen receptor can decrease activity of estrogen receptor on cancer.

● Tamoxifen - Selective Estrogen Receptor Modulators (SERMs) is a partial agonist.
- resembles estradiol and upon its binding to estrogen receptor is causes a difference in ER activity.

• causes enough conformation change to alter activity and partially inhibit binding.