Hormone Signaling Pathways

Question 1

Name common hydrophilic signaling molecules

Answer 1

Histamine, serotonin, dopamine, NE, E, insulin, glucagon, TSH

Question 2

Describe the mechanism that lipophilic hormones use to exert their effect on a cell.

Answer 2

Freely diffuse through the cell membrane where they will bind to a cytoplasmic nuclear receptor or diffuse directly into the nucleus. Their recpetors are of the family of DNA-binding transcription factors.

Question 3

What are the half lives of hydrophilic medications vs lipophilic medications?

Answer 3

Hydrophilic-> short

Lipophilic-> long

Question 4

Describe the activation of a trimeric G protein

Answer 4

Inactive state-> GDP bound to alpha, beta, and gamma subunits.
Active state-> GTP bound to alpha subunit only.

GEF exchanges GTP for GDP-> activation
GAP removes P->inactive

Question 5

What does activation of the Gs GPCR subunit result in?

Answer 5

Gs-> stimulates adenylate cyclase, which will activate PKA.

Question 6

What does activation of the Gi GPCR subunit result in?

Answer 6

Gi-> inhibition of adenylate cyclase, no cAMP produced.

Question 7

What does the activation of the Gt GPCR subunit result in?

Answer 7

Gt-> stimulation of hydrolysis of cGMP via phosphodiesterase.

Light triggers this GPCR

Question 8

What does the activation of the Gq GPCR subunit result in?

Answer 8

Gq-> activation of PLC which leads to second messenge IP3. Results in release of Ca2+ from ER/SR and activation of PKC. Ca2+ will bind to calmodulin-complex which activates both CaM kinase and MLC kinase.

Question 9

What receptor does epinephrine bind to and what is the result?

Answer 9

Gs-beta adrenergic receptor. Cause relaxation of bronchial and intestinal SM. Contraction of cardiac tissue.

Question 10

What receptor does histamine bind to and what is the result?

Answer 10

Gs histamine H2 receptor. Causes bronchocontriiton and symptoms of allergic rxn.

Question 11

How does the cAMP and PIP2 system alter gene expression?

Answer 11

cAMP-> PKA phosphorylates CREB which enters the nucleus to alter gene expression.

PIP2-> Ca2+ activates PKC which has a positive effect on gene expression.

Question 12

Describe the process of insulin regulation starting with glucose binding to the GLUT 2 receptor.

Answer 12

-intracellular glucose levels rise leading to increase ATP which will close the ATP dependent K channels. This causes depolarization and opens the voltage sensitive Ca2+ channels. Increased intracellular Ca2+ results in the exocytosis of insulin and c peptide.

Question 13

Name the constituents of the RAS-dependent signaling pathway and their effect.

Answer 13

GRB-2-> RAS-> leads to increased transcription of glucokinase. Also leads to increased glucose uptake and glycogen synthesis

Question 14

Name the constituents of the RAS-independent signaling pathway and their effect.

Answer 14

PI 3-kinase-> PKB-> Alterations in protein and enzyme activity (increased GLUT4 movement to plasma membrane, activation of glycogen synthase).

Question 15

Insulin acts via what type of receptor?

Answer 15

RTK

Question 16

Name the steps involved after insulin binds its receptor

Answer 16

1) binds RTK
2) autophosphorylation of receptor
3) Insulin receptor substrate (IRS) binds receptor and is phosphorylated on the tyrosine residues.
4) SH2-PI3 and SH2-GRB are activated.

Question 17

What are the 3 major domains of Nuclear Receptors?

Answer 17

Activation function 1 domain (AF1)
DNA binding domain (DBD)
Ligand binding domain (LBD)

Question 18

What is tamoxifen and its mechanism of action?

Answer 18

Estrogen receptor antagonist.

Recruits the nuclear-hormone receptor co-repress or (NcoR).

Question 19

Name the common lipophilic signaling molecules

Answer 19

Steroid hormones-> progesterone, estradiol, testosterone, cortisol, aldosterone.

Thyroxine

Question 20

Hydrophilic hormones signal via what mechanism?

Answer 20

Either GPCR or RTK