Cell Signalling

Question 1

Know the modes of cell-cell signaling.

Answer 1

• Endocrine – signal reaches target via circulation
• Paracrine – chemical fuses a short distance (stays in the neighborhood)
• Autocrine – secreting and target cell are the samed
• Juxtacrine – doesn’t secrete signal, but has it bound on extracellular
  surface. It reacts with target cell receptor. Requires cell-cell contact. Common in immune system.

Question 2

2. Trace the biosynthesis of NO.

Answer 2

• Acetylcholine released by nerve terminals in the blood vessel wall activates NO synthase in endothelial cells lining the blood vessel
• causes the endothelial cells to produce NO
• NO diffuses out of the endothelial cells and into the underlying smooth muscle cells
• binds to and activates guanylyl cyclase – produces cyclic GMP
• cGMP triggers a response that causes the smooth muscle cells to relax
• enhances blood flow through the blood vessel

Question 3

Identify the three main classes of cell-surface receptors.

Answer 3

ion channel receptor

enzyme-linked receptors – kinases, or bind kinases

• heptahelical receptors – 7TM, G-coupled protein receptors (GCPRs

Question 4

5. Describe G proteins and their function in membrane events.

Answer 4

G protein – binds guanine nucleotides (GTP and GDP) o GTP = active
 releases subunit which migrates to target protein o GDP = inactive
 channel closes

Question 5

Compare different heterotrimeric G proteins.

Answer 5

different g-proteins have different functions/targets o activation of ion channels
o Adenyl cyclase and cAMP – important in glycogenolysis  can cause diarrhea (see figure below)
o phosphatidyl inositolCa2+ release from ER- Cholera toxin – gets into cell because of B subunit
- B sticks to surface and internalizes the A-subunit via endocytosis
- A-subunit binds and keeps AC active all the time
o continuous production of cAMP o activates PKA
o activates ABC protein
o allows Cl- through
o intestine becomes hyperosmotic o water flows in (osmosis)
 causes diarrhea

Question 6

Describe the source of cAMP and other second messengers.

Answer 6

• Adenylyl Cyclase – converts ATPcAMP
  o AC – second messenger – released when g protein binds receptor
• diacylglycerol, phosphatidyl inositol, Ca2+
  o PLC – breaks down phospholipid (phosphatidyl inositol bisphosphate)
   DAG and IP3 – second messengers o IP3 – migrates to ER (high calcium content)
   causes release of Ca
   activates PKC
  o DAG – can further bind/activate PKC

Question 7

Trace the intracellular events leading to activation of nuclear transcription via protein kinase A.

Answer 7

• activated G-protein-linked receptor
• G protein -> adenylyl cyclase (AC)
• cAMP (AC, from ATP)
• PKAregulatory proteins

Question 8

Describe the role of PKA and PKC in signaling.

Answer 8

PKA – gets activated by cAMP
- goes after gene regulatory proteins
PKC – has many target proteins
- activated receptor phospholipase  diacylglycerol  PKC

Question 9

Compare ionotropic versus metabotropic effectors.

Answer 9

ionotropic effectors – produce very quick responses
- almost instaneous
- nicotinic receptor (muscle contractions)
metabotropic effectors – take seconds/minutes/hours
- goes through G proteins
o goes through an entire cascade

Question 10

Know the function of the ryanodine receptor and its association with malignant hyperthermia.

Answer 10

Ryanodine receptor – intracellular calcium channel
- when activated – releases calcium
- in some humans/animals, it gets out of control
o release too many calcium ions
o leads to phenomenon of heat release (malignant hyperthermia)

Question 11

Describe the activity of calmodulin.

Answer 11

Calcium binds calmodulin – inactiveactive

o binds to calmodulin kinase (CaM-kinase) – kinase becomes active

Question 12

Identify the role of PI 3-kinase in signal transduction.

Answer 12

• PI 3-kinase – adds phosphate group to the PIP
• conformational change causes gives molecule new function
• in figure, PIP molecule is phosphorylated giving it docking
  capabilities for certain molecules

Question 13

Identify the locations of PIP2, IP3 and PIP3.

Answer 13

• PIP2 – on cellular membrane
• IP3 – migrates to ER (high calcium content)
  o causes release of Ca2+
  o activates PKC
• PIP3 – on cellular membrane

Question 14

Know the relationship between IP3 and [Ca2+].

Answer 14

• IP3 – migrates to ER and causes release of Ca2+

- IP3 – turned on via G-protein-coupled signal cascade

Question 15

Compare the cellular responses of the MAP kinase pathway versus heptahelical pathway.

Answer 15

MAP kinase pathway (goes through RAS pathway)- tyrosine kinase receptor

• uses adaptor protein
• RAS protein (GTP-binding protein) – inactive
• exchanges GDP for GTP – activates RAS
• activity is transmitted downstream
• Active RAS – activates MAPKKK

Heptahelical Pathway (goes through G-protein pathway)
- g-protein coupled receptor
- primarily uses second messengers
- seven transmembrane alpha-helical
structures

Question 16

Know the function of oncogenes in cancer.

Answer 16

• Oncogenes – fine with no mutation
• Mutation – turned on and they cause cancer
  o mutant cannot hydrolyze GTP o continuous signal transmission
• Growth factor signaling pathways are relevant because they can cause cancer

Question 17

Retell the origin of the src gene.

Answer 17

RSV (Rous Sarcoma Virus)
- determined to cause cancer
- Src gene – normal in humans
- Viral Src gene is mutated form of our normal gene
- mutated form or our gene is an oncogene that leads to continuous signaling and cancer
o DNA replication o Cell proliferation o Differentiation