Zaidi cell signaling

Question 1

Define endocrine

Answer 1

the signal is transported through the blood and travels a long distance, therefore it is required to be long lasting

examples: epinephrine,

Question 2

Define paracrine

Answer 2

signal that diffuses to a neighboring cell or a different type; local and short lived

example: Leydig cells create and secrete testosterone which induces spermatogenesis by acting on Sertoli cells

Question 3

Define autocrine

Answer 3

secreting cells have receptors for what they are expressing OR they act on cells that are the SAME

example: cytokines

Question 4

Define direct/juxtacrine signaling

Answer 4

signal binds to the signaling cell which binds to the receptor on the target cell

SO the cell does not make the signal but is able to take the signal to the target cell

example: heparin-binding epidermal growth factor

Question 5

What are the receptors that are involved in hydrophobic signaling and what are the examples of things that use these pathways?

Answer 5

GPCR and receptor tyrosine kinases

epinephrine, insulin, glucagon

Question 6

What are the receptors for the lipophilic signaling? and what are the examples of things that use these pathways?

Answer 6

Lipophilic signals pass through the membrane so there are

1. cytoplasmic receptors which binds to the signal and takes it where it needs to go
2. nuclear receptors are present in the nucleus and the hormone allows more interaction with the additional proteins

regulate the TRANSCRIPTION of specific genes

examples: steroids, thyroid hormone, retinoids

Question 7

What are ways in which a signal is able to be “turned off”?

Answer 7

1. drop in hormone levels- if there are not a lot of ligands floating around, then there will not be as much receptor activity (drop is adenylyl cyclase activity, decreased cAMP, and decreased PKA activity
2. remove the signaling molecule: phosphodiesterase removes cAMP and cGMP
3. receptor sequestration: endosome
4. receptor destructions : endoscopes and lysosomes (proteases)

Question 8

What are the variations in GPCR signaling?

Answer 8

Gs: stimulates adenylate cyclase
Gt: stimulates cGMP phosphodiesterase
Gi: inhibits adenylate cyclase
Gq: activates phospholipase c

Question 9

What kind of G protein is involved in the pathway involving epinephrine? What kind of receptor is it? And what is the physiological response?

Answer 9

• Gs protein
• B-adrenergic receptor

1. relaxation of the bronchial and intestinal smooth muscle
2. contraction of the heart muscle
3. Increase breakdown of TAGs in adipose
4. Increase breakdown of glycogen in the liver and muscle
5. Increased glycolysis in the muscle

Question 10

What kind of G protein is involved in the pathway involving histamine? What kind of receptor is it? And what is the physiological response?

Answer 10

Gs protein
histamine H2 receptor

1. bronchoconstriction and sx of allergic reactions

Question 11

What kind of G protein is involved in the pathway involving epinephrine/norepinephrine? What kind of receptor is it? And what is the physiological response?

Answer 11

Gi
alpha-adrenergic receptor

1. constriction of smooth muscle

Question 12

What kind of G protein is involved in the pathway involving dopamine? What kind of receptor is it? And what is the physiological response?

Answer 12

Gi
Dopamine D2 receptor

1. increased heart rate

Question 13

What kind of G protein is involved in the pathway involving acetylcholine? What kind of receptor is it? And what is the physiological response?

Answer 13

Gq
Muscarinic acetylcholine M3 receptor

1. bronchoconstriction and stimulation of salivary glands

Question 14

What kind of G protein is involved in the pathway involving light? What kind of receptor is it? And what is the physiological response?

Answer 14

Gt
Rhodopsin

1. vision

Question 15

What is the role of cGMP phosphodiesterase?

Answer 15

hydrolyzes cGMP to 5’-GMP

Caffeine inhibits this activity, and leads to an accumulation of cAMP, leading to the increased heart rate

Question 16

Describe an erection in terms of cGMP PDE

Answer 16

inhibitors or PDE increase the concentration of cellular cGMP and prolongs its effects for a greater amount of time which leads to smooth muscle relaxation and vasodilation, resulting in an erection

Question 17

Describe how cholera toxin works

Answer 17

Inactivation of Gs(alpha)

-secondary to a consumption of contaminated water

• covalent modification of alpha subunits of Gs
• ADP ribosylation of Arg in Gs alpha and decreases the GTPase activity
• Gs alpha remains in its active form and keeps stimulating the adenylate cyclase, which results in an overproduction of cAMP

Chloride channels are opened, which leads to a a loss of electrolyte and water which leads to diarrhea

Question 18

Describe the mechanism and the effects of pertussis toxin on the airway epithelial cells

Answer 18

• pertussis toxin prevents the activation of Gi(alpha)
• the alpha subunit is not able to be taken away from the other subunits of the G protein complex
• less inhibition of AC and an overproduction of cAMP, which leads to the loss of fluids in the cells with excessive mucous secretion, which presents as whooping cough

Question 19

Describe how nitric oxide effects the body

Answer 19

relaxes the smooth muscles

• NO diffuses to the neighboring muscles and activates guanylate cyclase, which produces cGMP
• the cGMP that is produced results in smooth muscle relaxation and vasodilation

Question 20

Describe how nitroglycerin works

Answer 20

Decomposes to form NO, which lowers blood pressure

Question 21

Describe the effects of antihistamines on GPCR signaling

Answer 21

antihistamines are lipophilic molecules and act to prevent the binding of histamine to the H1 receptors

examples diphenhydramine, zyrtec, etc

Question 22

Describe monomeric G proteins

Answer 22

• have a single polypeptide chain
• control a diverse set of processes: cell proliferation, intracellular vesicular traffic, survival and apoptosis, cell shape and polarity, membrane transport and secretion
• intrinsic GTPase activty

subfamilies: Ras, Rab, Rho, Ran

Question 23

Describe the correlation between Ras and cancer

Answer 23

30-50% lung cancers and 90% pancreatic cancers are associated with mutations in RAS

these mutations decrease the GTPase activity and keep it in an active form, which can lead to cancer

Question 24

Describe neurofibromatosis

Answer 24

tumors that grow on the nerve tissue

inactivating mutation in the NF-1 gene, which encodes a GAP for RAS which keeps everything growing uncontrollably, resulting in tumors

Question 25

How are RTKs associated with cancer?

Answer 25

When there are mutated RTKs or an over expression, there is excessive signaling, which leads to cancer

can target the RTKS for example the HER2 target of Herceptin in breast cancer