lecture 17 signal transduction

Question 1

pathway

Answer 1

signal -> receptor -> transduction -> response

Question 2

categories of signals

Answer 2

endocrine, paracrine, neurotransmitters

Question 3

endocrine factors

Answer 3

hormones that travel throughout bloodstream to a distant organ

Question 4

paracrine factors

Answer 4

released from one organ to a nearby organ. or itself if autocrine

Question 5

neurotransmitters

Answer 5

released across synapses (gap between neurons)

Question 6

what’s special about acetyl choline and what it does?

Answer 6

same signal causes different reactions in different cells. acetyle choline in heart decreases contractions, in salivary gland causes secretion, in skeletal muscle causes muscle contractions

Question 7

classes of receptors

Answer 7

nuclear hormones, ligand gated ion channels, G-protein receptors, enzyme-linked receptors

Question 8

nuclear hormone receptors

Answer 8

receptors for steroid hormones

Question 9

ligand gated

Answer 9

nerves communicating w/ nerves and muscles

Question 10

G-protein coupled receptors

Answer 10

traverse the membrane with 7 alpha helices. Bind GDP/GTP

Question 11

enzyme-linked receptors

Answer 11

membrane proteins that dimerize then recruit protein kinases, OR dimerize and then become protein kinases

Question 12

T/F: Transduction mechanisms differ for each class of receptor

Answer 12

true

Question 13

what happens with hydrophobic vs hydrophilic signals?

Answer 13

hydrophobic signals diffuse across the cell membrane, while hydrophilic signals do not enter the cell, and receptors are on the surface

Question 14

what’s the mechanism going on for hormone receptors?

Answer 14

steroid hormones diffuse across membrane. hydrophobic. receptor waits for them in either the cytoplasm or the nucleus, recognizes a target sequence on their DNA, and changes transcription of genes accordingly

Question 15

what are the two domains that the nuclear hormone receptors have?

Answer 15

hormone binding domain and DNA binding domain.

Question 16

what happens that activates the intracellular receptor protein for nuclear receptors?

Answer 16

the signal binds and causes a conformational change. this brings the whole molecule (activated receptor) to the nucleus where it can find its target gene

Question 17

ligand gated channels

Answer 17

binding of a ligand such as acetylcholine opens the channel to allow the facilitated diffusion of a specific ion. ex: acetylcholine opens sodium channel in muscle cells

Question 18

G-protein coupled receptors

Answer 18

signal binds as a ligand in the 7-alpha helices. binding causes G protein to change conformation, dumping out a GDP and dissociating from beta and gamma unit, taking up a GTP. then, activated receptor can trigger adenylate cyclase, trigger cyclic AMP, etc

Question 19

cyclic AMP is what kind of molecule?

Answer 19

allosteric effector molecule . activator of protein kinase

Question 20

how do G-proteins shut themselves off ?

Answer 20

through hydrolysis of GTP, or through epinephrine concentration just falling off

Question 21

enzyme-linked receptors

Answer 21

phosphorylates stuff. either itself or a target protein to activate them. tyrosoine kinase receptor is already a kinase itself, while growth hormone receptor acts on behalf of RTK to phosphorylate stuff

Question 22

how do enzyme linked receptors actually work , in terms of the activation?

Answer 22

ligands dimerize the receptor, which enables it to bind to and activate other kinases

Question 23

how does EGF receptor work?

Answer 23

The binding of epidermal growth factor (EGF) to its receptor leads to cross-phosphorylation of the receptor. The phosphorylated receptor binds Grb-2, which, in turn, binds Sos. Sos stimulates the exchange of GTP for GDP in Ras. Activated Ras binds to protein kinases and stimulates them

Question 24

What is ras?

Answer 24

Ras activates kinases that affect growth and cell division

Question 25

Growth Factor receptors (GF-RTKs)

Answer 25

Growth Factor receptors (GF-RTKs) autophosphorylate and may recruit proteins that activate Ras-GDP by removing the GDP so GTP binds.

Question 26

Transduction Mechanisms

Answer 26

A. voltage change (electrical potential change) leads to neuronal signaling and muscle contraction.
B. Increasing concentration of “second messengers” that act to alter target protein shape when bound
C. Activate or inhibit transcription such as steroid binding to nuclear receptors. Hormone-receptor complex binds promoters on DNA
D. Activation of kinases that phosphorylate other proteins or enzymes to activate or inhibit them

Question 27

how does increasing the concentration of second messengers act as a transduction mechanism?

Answer 27

alters target protein shape when bound

Question 28

name the 2 ways that 7TM does transduction

Answer 28

1) activates adenylyl cyclases which creates cAMP from ATP. cAMP is an allosteric activator of protein kinase A
2) releases IP3 which opens a calcium ion channel and activates proteins such as calmodulin

Question 29

name some commonly used second messengers

Answer 29

cAMP, calcium ion, IP3, DAG

Question 30

why do we care about calcium ion? what does it do that is special?

Answer 30

Ca2+ is an important second messenger in eukaryotic signal transduction pathways. It triggers exocytosis of secretory vesicles in neurons and actin-myosin interaction in muscle contraction. It also binds calmodulin, a common Ca2+ sensor.

The Ca2+-calmodulin complex activates a variety of biochemical targets, including pumps, such as the plasma membrane Ca2+ ATPase, and the calmodulin-dependent protein kinase (CaM kinase).

Question 31

what kind of receptor would already contain a tyrosine kinase domain in their covalent structure

Answer 31

receptor tyrosine kinases (RTK)

Question 32

___was the first known case of a virus causing cancer (oncogenic virus).

Answer 32

Ras (Rous avian sarcoma virus)

Question 33

how does steroidal binding to nuclear receptors transduction mechanism work?

Answer 33

After diffusing across the bilayer, the hormone binds noncovalently to its receptor waiting in the cytoplasm (or in the nucleus). The hormone-receptor complex finds specific target genes in the DNA and activates transcription of a specific gene (e.g., estrogen activates ovalbumin gene to make this protein for chick egg whites

Question 34

how does the kinase transduction mechanism work with growth factors?

Answer 34

Growth Factor receptors (GF-RTKs) autophosphorylate and may recruit proteins that activate Ras-GDP by removing the GDP so GTP binds. Ras activates kinases that affect growth and cell division.

Question 35

how does the kinase transduction mechanism work with receptor tyrosine kinases? ex: insulin

Answer 35

The polypeptide hormone insulin is secreted when the blood is rich in glucose. Receptor dimers form on insulin binding, leading to cross-phosphorylation and activation of the kinase domains. The activated kinase of the insulin receptor phosphorylates insulin-receptor substrates…

to creates PIP3. PIP3 activates Protein Kinase B (PBK) which activates glycogen synthesis enzymes and increases glucose transporters on the plasma membrane

Question 36

termination of transduction pathway; phosphate reason

Answer 36

Phosphatases remove the activating phosphates from target proteins, cAMP is clipped by phosphodiesterase to form AMP

Question 37

terminatin of transduction response pathway; GTP

Answer 37

G protein response is self-limiting because alpha subunit that holds the GTP is also a slowly acting GTPase.