Cell Comm 2 - Dr White

Question 1

Question 2

What is the major difference of “G alpha q” and “G alpha o” compared to other G proteins?

Answer 2

once GCPR attaches to this they associate with Phospholipase C not Adenyly Cyclase

Question 3

How do IP3, DAG, Ca2+ associate with one another?

Answer 3

Phospholipase C cleaves membrane protein in PIP 2

• PIP2 procudes IP3 and DAG (2nd messengers)
• IP# triggers release of Ca2+ from ER via binding to an IP#-gated Ca2+ channel + triggers opening
• Ca2+ reeased into cytosol
• Ca2+ (Also 2nd messenger)
• CA2+ and DAG bind to protein kinase c (PKC)
• Conformational change in PKC = activation
• PKC phopshorylates a variety of membrane and subrstrates

Question 4

What is calciums other function as a 2nd messenger

Answer 4

Binds to Calmoduin

Calmodulin binds to other proteins to activate their functions

Question 5

What are the receptors , G proteins, Targets, 2nd messenagers, and effectors all relating to signal transduction via G proteins

Answer 5

Receptors: specific

G proteins: Gas, Gai, Gao, Gaq, Golf

Targets: adenylyl cyclase, phospholipase C

2 nd messengers: cAMP, DAG, IP3, Ca2+

Downstream effectors: PKA, PKC, gatedion channels

Question 6

What are the other 3 types of singal transduction?

Answer 6

Tyosine Kinases

Jak Stat Receptors

Serine/threomime kinases

Question 7

What are receptor Tyrosine Kinases?

Answer 7

• Signal transduction
• Enzyme linked receptors and enzymatic domain is in cytoplasmic tail of integral embrane protein
• RTK is used for response to growth factors to mediate growth factor signals
• cells with RTK are in contact indirectly with blood so add back serum factors and result is growth! (no serum = no growth)
• Cytoplasmic domain transmits signal through tyrosine kinase domain
  
  • adds phosphate to tyrosine on proteins

Question 8

What are the growth factors?

Answer 8

EGF = epidermal growth factos

PDGF - platlet dervived growth factor

NGF - nerve growth factor

FGF fibroblast growth factor

IGF-1 insulin like growth factor 1

all cause cells to grow and proliferate in cell culture and growth factors based on where its discovered but found in lots of cells

Question 9

What is the function of RTK?

Answer 9

Binds to growth factor through extracellular domain

Signal through cytoplasmic domains (contains tyrosine kinas)

Phosporylates protein on tyrosine AA residues for activation

Question 10

What are the steps of signal transduction through Receptro Tyrosine Kinase?

Answer 10

1. Ligand binds to RTK
2. Dimerization of 2 receptor monomers
3. Autophosphorylation
4. Receptor associates/binds to proteins w. the SH2 Domain (GRB2 in this case)
5. The SH3 domain in GRB2 binds to SOS “son of sevenless”
6. SOS binds to RAS
7. RAS binds to RAF
8. Map is initiated
9. leads to changes in protein activaty or gene expression

Question 11

What is SOS protein?

Answer 11

Son of sevenless

GEF and adds GTP to Ras

Name comes from R7 not being a gene that causes death when knoced out

Question 12

What are the Steps of the Map Kinase Cascade?

Answer 12

1. ras initates MAP kinase cascade
   * “Mitogen activated protein Kinase” = cell proliferation
2. MAP kinase Kinase Kinase “RAF”
3. MAP kinase Kinase “Mek”
4. Map Kinase “Erk”
5. Nucleus
6. Increased gene transcription
7. (no regulation leads to cancer)

Question 13

SUMMARY SLIDE BOISSSSS

Answer 13

• Growth factor binds to receptor
• Receptor becomes active tyrosine kinase
• Autophosphorylates
• Binds to Grb2 – SOS – Ras – Raf – gene transcription through MAP kinase pathway
• Many signaling molecules are protooncogenes that can mutate into oncogenes and cause cancer

Question 14

What are the steps for Jak - STAT receptors?

Answer 14

More direct route for impacting transcription

Erythropoeitin EMplys jak STAT to initiate signaling

1. Ligand binds to receptors - dimerie - then binds JAKS (janus Kinases)
2. JAKs phosphorylate each other
   JAKs phosphorlate receptors
3. Receptor binds and phosphorylates STATs (signal transducer and Activators of Transcription Proteins )
4. STATs separate from receptors, dimerize and enter nucleus - binds to DNA and causes transcription of terget genes

Question 15

What is the Serine Threonine Receptor and Smad

Answer 15

ANother more direct route: R-smad = receptor specfific Smad and forms complex with Co-Smad: Common Smad

Activated receptor by (phosphorlaytion) binds to R-Smad (receptor specific) and Phosphorlates R-Smad

R-Smad binds to Co-Smad (common Smad) and moves into Nucleus to impact transcription of target genes

EX: HEPCIDIN (IRON metabolism)

Question 16

What is hereditary hemachromatosis

Answer 16

uncontrollable iron absorption

iron overloading

toxic levels of iron get depositied in organs

Question 17

What aids in transport of iron into Enterocytes? (intestinal cells)

Answer 17

DMT1 - Iron into intestinal cell

Ferroportin - iron out of intestinal cell and into blood

Hepcidin a protein made in the liver regualtes iron homeostasis

Question 18

How does Hepcidin work?

Answer 18

Hepcidin exerts its regulatory effect by binding to ferroportin

Ferroportin is receptor for hepcidin

Hepcidin binds to ferroportin which causes internalization of ferroportin which is destroyed by proteolysis

high [Fe] - hepcidin expression is up and ferroportin levels are down

low [Fe] - hepcidin expression is down and ferroportin is up

Question 19

What is the cause of hereditary hemochromatosis ?

Answer 19

Genetic Iron overloading

1. Autosomal ressive
   
   1. (most common autosomal recessive dieasse genes in man)
2. mutations in HFE gene ( hereditary iron)
3. Cys 282 to Tyr (C282Y)
4. HFE protein membrane bound that associates with TfR2 and expresses Hepcidin
5. Found in Liver
6. HFE binds to transferrin receptor (TfR)

Question 20

What Pathway does Hfe work through?

Answer 20

Its works through smad pathway to induce hepcidin expression

If Hfe is mutated it cannot assocate with TfR2 (trans-ferrin Receptor 2) which means no hepcidin expression thus causing iron overloading