2C- Cell Signaling

Question 1

What are chemical messengers?

Answer 1

substances that transmit messages between cells

Question 2

What is a general sequence of chemical messenger action?

Answer 2

chemical messenger secreted by a cell in response to a stimulus –> diffuses through blood or EC fluid to the target cell –> receptor binds to it –> binding of the messenger to the R elicits a response –> signal ceases and is terminated

Question 3

What are the events of a chemical synapse?

Answer 3

Question 4

How does Myathenia gravis affect cell signalling?

Answer 4

It’s an autoimmune disease where the body makes antibodies against the NmAchR.

Once they bind to the R they don’t allow Ach to bind, thereby creating muscle weakness.

Question 5

What are the differences between endocrine, paracrine and autocrine messengers?

Answer 5

Endocrine - secreted by a cell into the blood and aacts on target cells a distance away

Paracrine- secreted by a cell and acts on neighboring cells. This is like the Ach synapse.

Autocrine- secreted chemicals from 1 cell act on the same cell

Question 6

What are the 2 major messengers of the nervous system?

Answer 6

Neurotransmitters- nitrogen containing molecules that can be AA’s or derivatives of AA’s.

Neuropeptides- small peptides secreted by neurons that act as neurotransmitters at synaptic junctions or are secreted into the blood as neurohormones.

Question 7

What are the 4 major types of hormones?

Answer 7

Polypeptide hormones- like insulin

Catecholamines- like epinephrine

Steroid hormones- derived from cholesterol

Thyroid hormone- derived from Tyrosine

Question 8

What are cytokines?

Answer 8

They are messengers of the immune system

Small proteins that regulate a network of responses designed to kill invading microorganisms

Question 9

What are eicosanoids?

Answer 9

They control cellular function in response to injury

All derived from arachidonic acid

Almost every cell in the body contains them and act in mainly paracrine or autocrine functions.

Question 10

What is the mechanism of membrane receptors?

Answer 10

They have extracellular binding domains

They are typically polar molecules that cannot travel across the membrane

They bind to a cell surface receptor and elicit an intracellular response

Catecholamines fall into this category

Question 11

What is the mechanism of cytoplasmic receptor action?

Answer 11

They are lipid soluble, so they pass through the lipid bilayer

bind to a cytoplasmic R –> R goes through a conformational change –> dissociates from the heat-shock protein –> receptors dimerize –> travels to the nucleus –> acts as a transcription factor on the hormone response element of DNA

Question 12

What is the mechanism of nuclear receptors?

Answer 12

The lipophilic messenger binds to the R on DNA and changes its activity anmd its ability to associate with or dissociate from DNA

Question 13

What is the mechanism of ion-channel receptors?

Answer 13

These work like the NmAchR’s discussed before

Signal transduction consists of conformational change when the ligand binds –> opens –> allows ions to flow through

Question 14

What is the mechanism of kinase receptors?

Answer 14

protein kinases transfer a phosphate group from ATP to the hydroxyl group of a specific amino acid side chain in the protein

basically, when the L binds to the R, the intracellular portion of the R is a kinase and is activated

The kinase then phosphorylates AA’s, proteins or itself.

Question 15

What is the mechanism of heptahelical receptors?

Answer 15

They contain 7 transmembrane helices

Most common type of plasma receptor

work through 2nd messengers such as cAMP

Question 16

What is the general mechanism of tyrosine kinase receptors?

Answer 16

exist as monomers with a single membrane spanning helix –> 1 L binds 2 R’s –> R’s dimerize –> intracellular tyrosine kinase phosphorylate each other on certain Tyr residues –> form binding sites for signal transducer proteins

Question 17

Explain the pathway of the RAS/MAP kinase

Answer 17

Question 18

Go through the pathway of the insulin receptor and its signal transduction

Answer 18

the insulin tyrosine kinase R exists as a dimer –> insulin binds –> R’s autophosphorylate –> insulin receptor substrate binds and is phosphorylated –> PI3K binds and is activated, SH2 binds and RAS/MAP is activated, PLCý binds and is activated

PI3K activates PKB

Question 19

What are the steps of the Gs pathway?

Answer 19

Question 20

What are the steps of the Gq pathway?

Answer 20

Question 21

12. Describe the two forms of guanylate cyclase that can be activated to cause vasodilation. Explain how NO can stimulate this pathway.

Answer 21

-Membrane bound guanylly cyclase receptors convert GTP to second messenger 3’,5’-cyclic GMP (analogous to cAMP). These receptors directly make cGMP in response to binding the appropriate ligand (unlike heptahelical receptors which need G protein singling to adenylyl cyclase to produce cAMP). CGMP is degraded by membrane-bound phosphodiesterase (target of some drugs). Elevated cGMP activates protein kinase G which then phosphorylates target proteins to propagate the response.

-A soluble form of guanylyl cyclase is located in the cytoplasm is receptor for the nitric
oxide neurotransmitter/neurohormone. NO is a lipophilic gas that is able to diffuse into
the cell and is an exception to the rule the intracellular receptors are Gene transcription factors.

-GMP elevating drugs have been used in humans to treat a variety of disorders, such
as angina pectoris (glycerol trinitrate decomposes to NO, which activates a guanylyl
cyclase),heart failure (using nesiritide,which is synthetic BETA natriuretic
peptide,a ligand for activation of a guanylyl cyclase receptor),and erectile dysfunction (through
drugs that inhibit a cGMP phosphodiesterase, such as sildenafil).