Receptors and Signaling

Question 1

Hydrophilic Signaling which receptors

Answer 1

G protein Coupled receptors (GPCR)

Receptor Tyrosine Kinase (RTK)

Question 2

Lipophilic Signaling Receptor

Answer 2

1) Cytoplasmic Receptors
- inactive complex with HSP 90
- bind to DNA sequence HORMONE RESPONSE ELEMENT (HRE) to go to nucleus

2) Nuclear receptors

Question 3

G-Protein Coupled Receptors Component

Answer 3

1) Extracellular Domain
2) Transmembrane Domain
7 alpha helix
3) Intracellular Domain

Question 4

Trimeric G Protein

Answer 4

inactive G protein - GDP has ABY

active G protein- GTP bound alpha unit separates from beta and gamma subunits

Question 5

Activation/Inactivation Cycle of Trimeric G Protein

Answer 5

GEF activates

GAP inactivates

Question 6

Gs GPCR Signaling

Answer 6

stimulate adenylate cyclase

signal molecule bind to GPCR -> active GTP-> increase AC-> increase cAMP-> activate pka-> phosphorylation

epinephrine/ histamine for beta- adrenergic receptors

Question 7

Gi GPCR Signaling

Answer 7

inhibit adenylate cyclase

signal molecule bind to GPCR-> active GTP -> inhibit AC-> no cAMP-> pka not activated

epinephrine/nonephrine in alpha adrenergic receptor

Question 8

Gt GPCR Signaling

Answer 8

stimulate cGMP phosphodiesterase

light-> GPCR-> active GTP-> cGMP PDE-> degrade cGMP to 5’GMP

light for vision

Question 9

Gq GPCR Signaling

Answer 9

activate phospholipase C

signal molecule bind to GPCR-> active GTP-> activate PLC-> activate PIP-> active DAG and IP3-> release ca2+ in SR-> increase pkc-> activate

Ach

Question 10

Viagra and NO

Answer 10

vasodilation and smooth muscle relaxation

prevent degradation of cGMP to 5’ GMP, inhibit cGMP Phosphodiesterase

more cGMP

Question 11

Chlore and Pertussis

Answer 11

Cholera- covalent modification ADP RIBOSYLATION of Arg, decrease GTPase activity-> Gs still activate->AC activation-> overproduction of cAMP

Pertussis- ADP RIBOSYLATION of Cys on Gs-> less inhibition of AC-> overproduction of cAMP

Question 12

Mechanics of H20 in relation to diseases (CFTR)

Answer 12

activate AC-> increase c AMP-> activate CFTR-> leads to increase Cl -> increase in Na+ for NaCl-> increase water secretion

Question 13

Signal Desensitization

Answer 13

Receptors are ignored or turned off

Receptor Sequestration: endosomes
Receptor Destruction: Endosomes + lysosomes ( proteasome)

Question 14

Grks

Answer 14

G protein receptor kinase
Inactivates gcprs
Uses arrestin to create loop to prevent conversion of g alpha gdp to g alpha gtp

Question 15

Rtks components

Answer 15

ECD
Transmembrane- single alpha helix
ICD- have tyrosine kinase activity

Question 16

Rtks signaling

Answer 16

1) signal binds to ecd -> conformational change
2) auto phosphorylation
3) phototyrosine binds to adaptor and docking protein ( sh2 domain of grb2)
3) downstream via ras dependent or ras independent
- grb2-> sos -> ras -> raf