Signal transduction

Question 1

What is meant by signal transduction?

Answer 1

It is the overall process of converting the extracellular signals into intracellular responses and explaining how the cells communicate with each other

Question 2

What are the key players of signal transduction?

Answer 2

1) Signaling molecules (some are long distance, and some act on the immediate neighbor cell)

2) Receptors

3) Signal transduction proteins and second messengers

4) Effector proteins

• Most of our cells are both emitters and recievers

Question 3

What is the importance of signal transduction?

Answer 3

• it is important in order for the cell to undergo:

1) Growth

2) Survival

3) Differentiation

4) Migration

5) Proliferation

6) Apoptosis

Question 4

What are the different modes of cell communication?

Answer 4

• Communication is either between the nervous or endocrine system

1) Direct

• Cell-cell (Notch, Cadherin)

2) Indirect

• Paracrine (cytokines)
• Synaptic (Neurotransmitters)
• Endocrine

Question 5

What are the different forms of intercellular signaling?

Answer 5

1) Direct: Contact-dependent signaling, which requires the cell to be in direct membrane-membrane contact (like when APC binds to T-CELL)

2) Indirect:

2a) Paracrine signaling

2b) Synaptic signalling

2c) Endocrine signaling

Question 6

What is meant by paracrine signaling?

Answer 6

They are chemicals (like eicosanoids, prostaglandins, and cytokines) that are produced by a cell in order to perform a function in the neighboring cells

Question 7

What is meant by synaptic signaling?

Answer 7

Performed by neurons, which transmit neurotransmitters at synapses, which are located far from the cell body

Question 8

What is meant by endocrine signaling?

Answer 8

Endocrine cells secrete hormones into the bloodstream which are then distributed widely throughout the body

Question 9

What are the different classifications of hormones?

Answer 9

• Secreted into the bloodstream by the endocrine cells

1) Protein/Peptide hormone

Prohormone - stored in secretory granules before being released via exocytosis (like insulin)

2) Steroid hormone

• Derived from cholesterol, synthesized in the adrenal cortex, gonads, and placenta

3) Amino Acid-Derived Hormones

• Amino-acid-derived hormones (from tyrosine) It include catecholamines, norepinephrine, epinephrine, dopamine, and thyroid hormone

Question 10

What are the different classes of hormones?

Answer 10

1) Water-soluble

2) Lipid-soluble

Question 11

What are the characteristics of water-soluble hormones?

Answer 11

1) Its receptor is inside the cell membrane

2) The second messenger involves protein kinase activation

3) It takes minutes for the protein phosphorylation to occur modifying the activity of the enzyme

4) It controls gene expression through proteins like cAMP response element binding protein (requires hours)

5) It includes the peptide/protein hormone + NE, EPI

Question 12

What are the characteristics of lipid-soluble proteins?

Answer 12

1) Their receptor is inside the cell

2) The hormone-receptor complex binds the hormone response elements (HRE) of the enhancer regions in the DNA

3) It controls gene expression (requires hours)

4) Example includes: steroids, thyroxine, and retinoic acid

Question 13

How are peptide hormones synthesized?

Answer 13

1) mRNA on the ribosome of the ER binds amino acids into a peptide chain called a preprohormone, the chain is directed into the lumen of the ER through a signal sequence of amino acids

2) Enzymes in the ER chop of the signal sequence, creating an inactive prohormone

3) The prohormone passes from the ER through the Golgi apparatus

4) The secretory vesicles containing the enzymes and prohormones bud off the Golgi, the enzyme chops the prohormone into one or more peptides and additional peptide fragments

5) Through exocytosis the secretory vesicle releases its contents into the extracellular space

6) The hormone then moves through the blood into its target organ

Question 14

Give me the most imp FYI regarding the synthesis of peptide hormones

Answer 14

1) Stored in membrane-bound granules and released by exocytosis

2) Circulates in the blood unbound, and they are relatively polar

3) They are readily digested by the GI, thus not administered orally

4) They usually have a cell membrane receptor

Question 15

In what form are the peptide hormones stored?

Answer 15

As preprohormone

• The endoplasmic reticulum will remove the pre and transform it into a pro in the cisternal space
• The Golgi apparatus will cleave insulin from the proinsulin

Question 16

What are the different types of receptors?

Answer 16

1) Extracellular receptor (water-soluble ligands)

2) Intracellular receptors (for the lipid-soluble ligand)

Question 17

What are the different types of extracellular receptors?

Answer 17

• For the water-soluble ligands

1) Receptor enzyme (catalytic receptors)

2) Receptors involving second messenger molecules

3) Lignad-gated ion channels (Neurotransmitter receptor linked to ion channels “ionotropic”)

Question 18

What are the types of intracellular receptors?

Answer 18

• For the lipid-soluble ligands

1) Cytosolic (glucocorticoids receptors)

2) Nuclear receptor (steroids, thyroid)

• if the receptor is in the cytosol the hormone will bind to the receptor and then translocate to the nucleus

Question 19

Describe the transduction of cellular signal by intracellular receptor

Answer 19

• Vitamin D, Steroidal Hormones, retinoic acid, and thyroxine, all of act via intracellular receptor
• The receptor-ligand complex enters the nucleus and binds to specific regions of the DNA, increasing the expression of a specified gene

Question 20

Describe the process of transduction by cell-surface receptors

Answer 20

1) Signal transduction is initiated by the binding of hormones to the receptor located in the plasma membrane

2) The signal will interact with the receptors, the activated receptors will interact with the cellular machinery producing a second signal/change in the activity of cellular protein which will then change the metabolic target of the target organ

Question 21

What are the different classes of cell-surface receptors based on their signal transduction mechanism?

Answer 21

1) Ligand-gated ion channels (neurotransmitters linked to ion channels like the cholinergic nicotinic receptors)

2) Receptor enzyme (like the insulin receptors)

3) Receptors involving second messenger molecules (catalytic receptors like the a and b-adrenoceptors)

Question 22

What is the mechanism of action of the ligand-gated ion channels

Answer 22

• ION channels that are regulated by hormones

1) Ach will bind to receptors on the muscle cells, leading to the opening of cation (Ca+, Na+) channels

2) Na+ will flow in, depolarizing the receiving cell, initiating another AP or contraction of the muscle cell

Question 23

Describe the mechanism of action of the receptor enzyme

Answer 23

• It has two alpha subunits in its external part, and a 2b-subunit that spans both spaces (extra and intracellular)- They are transmembrane catalytic receptors that have an inherent tyrosine kinase activity as part of their structure
• On the extracellular surface, they have a ligand-binding domain on the surface of the plasma membrane and an enzyme-active site on the cytosolic side
• The binding of ligand “Insulin” activates tyrosine kinase, which will phosphorylate the tyrosine residue
• Insulin receptor is a prototype for this type of receptor, bids in the alpha subunit found extracellularly

Question 24

What is the type of receptor for insulin?

Answer 24

Receptor enzyme

Question 25

what are the different types of second messenger molecule receptor

Answer 25

1) Adenylate cyclase system

2) Phospholipase C

Question 26

What is the mechanism of action of the adenylate cyclase receptor?

Answer 26

• It is a receptor coupled to a G-protein, a typical example is the adrenergic receptors (b-receptor)

1) Epinephrine, glucagon can bind to its specific receptor

2) The occupied receptor causes the replacement of GDP bound to Gs by GTP activating the Gs protein

3) The alpha subunit of the Gs protein moves to the adenylyl cyclase and activates it

4) Adenylyl cyclase will convert ATP into cAMP (2nd messenger)

5) cAMP activates PKA (protein kinase “it has 4-subunits 2 catalytic and 2 regulatory”), phorphorylating cellular protein via PKA elicting a cellular response to the epinephrine

6) The action of cAMP will be terminated via phosphodiesterase

Question 27

What is the mechanism of action of the phosphatidylinositol system?

Answer 27

1) Hydrolysis of phosphatidylinositol via phospholipase C, producing Diacylglycerol and Inositol tri-phosphate (where both f them act as a second messenger)

• IP3 (Inositol 1,4,5-triphosphate) increases Ca2+ concentration in the muscles
• Diacylglycerol will activate protein kinsae (like protein kinase C)

Question 28

What are the different terminating signals?

Answer 28

1) Phosphatases

2) GTP hydrolysis

3) Protein degredation

4) Receptor endocytosis

5) Inhibition of gene transcription

Question 29

What are the different ways of measuring hormone levels in body fluids?

Answer 29

1) ELISA (Enzyme-linked immunosorbent assay)

2) Chromatographic assays

3) Mass spectroscopy

Question 30

What is meant by signal amplification?

Answer 30

• When an enzyme activates other enzymes and the cycle continues