Signal Transduction Pathways

Front 1

Signal transduction

Back 1

Mechanisms by which living cells detect, amplify, and proces extracellular signals into physiological response.

Front 2

What is signal transduction essential forM?

Back 2

responding to external stimuli, intercellular communication, and biochemical pathways

Front 3

What are examples of diseases caused by abnormal cell signaling?

Back 3

asthma, cancer, diabetes, cystic fibrosis, atherosclerosis, cholera, whooping cought, diphtheria, retinitis pigmentosa...

Front 4

What are the types of extracellular messengers?

Back 4

Hormones, neurotransmitters, eicosanoids

Front 5

T3

Back 5

triiodothyronine

Front 6

t4

Back 6

thyroxine

Front 7

Hydrophilic vs lipophilic transport in blood

Back 7

Hydrophilic - free
lipophilic = transport protein

Front 8

Hydrophilic vs lipophilic half-life

Back 8

Hydrophilic - Short
lipophilic = Long

Front 9

Hydrophilic vs lipophilic receptor site

Back 9

Hydrophilic - Plasma membrane
lipophilic - Nucleus

Front 10

Hydrophilic vs lipophilic mechanism of action

Back 10

Hydrophilic - 2nd messenger
lipophilic - transcription factor

Front 11

What two major groups can extracellular messengers be put in?

Back 11

Water soluble and lipid soluble

Front 12

What are targets of extracellular messengers?

Back 12

Metabolic Enzyme
Ion Channels
Cytoskeletal proteins
Transcription factors

Front 13

Ser/Thr specific protein kinases (5)

Back 13

cAMP-dependent (PKA)
cGMP-dependent (PKG)
Protein Kinase C (PKC)
Ca/CaM-dependent (CaM-kinase)
Mitogen-activated (MAP-kinase)

Front 14

Tyrosine specific protein kinases
(5)

Back 14

EGF receptor
PDGF receptor
FGF receptor
Insulin receptor
Src Protein (NOT a receptor)

Front 15

Ser/Thr-PO4 specific protein phosphatases

Back 15

Type I, Type IIA, IIB, IIC

Front 16

Tyrosine-PO4 specific protein phosphatases

Back 16

CD45

Front 17

Different forms of cell signaling

Back 17

--Autocrine - acts on cell that released them (growth factors)
--Paracrine - acts on nearby cells (prostaglandins)
-- Endrocrine - acts on distant cels (insulin and epinephrine)

Front 18

G-protein coupled receptors require what?

Back 18

Hormone/neurotransmitter
Receptor
G-protein
Effector

Front 19

G-protein

Back 19

Has 7 domains, C-terminus is cytosolic. Membrane protein that binds GTP or GDP. Relays info from receptor to effector.

Front 20

Types of G-protein

Back 20

Monomeric (small) or heterotrimeric (has αβγ subunits)

Front 21

Which subunit on a G-protein gets activated/inactivated?

Back 21

The α-subunit

Front 22

Types of heterotrimeric G proteins

Back 22

Gs - stimulates AC
Gi - Inhibits AC
Gq - stimulates PLCβ
Gt (transductin) - Stimulates cGMP PDE

Front 23

What are effector proteins?

Back 23

Located in PM. Activated by alpha subunit of G protein. Generate 2nd messenger molecules. AC, PLCβ, PDE

Front 24

cAMP messenger system: AC

Back 24

Resting state Gs is trimeric and GDP is bound. Binding of hormone to receptor causes conf. change, GDP on receptor is changed to GTP. α-GTP activates AC generating cAMP in cell. GTPase hydrolizes α-GTP to α-GDP, terminates signal.

Front 25

Synthesis and Degradation of cAMP

Back 25

AC catalyzes cAMP from ATP. PDE breaks down cAMP.

Front 26

What inhibits PDE

Back 26

methylxanthines such as caffeine, theophylline. When present, they protect cAMP from hydrolysis, [cAMP increases,

Front 27

What activates AC?

Back 27

Forskolin - increases cAMP in cell

Front 28

Mechanism of action of cAMP

Back 28

cAMP stimulates PKA. PKA has two catalytic and two regulatory subunits. Without cAMP, all four are bound and inactive. 4 cAMP bind to catalytic subunits and activate enzyme (2 C subunits). These catalytic subunits phosphorylate Ser/Thr, causing gene expression.

Front 29

Regulation of AC

Back 29

There is a balance between inhibitory and stimulatory. Ex: Epi increases force of muscle contraction by stimulating Gs, which increases cAMP via AC. ch dampens Epi by stimulating Gi.

Front 30

What are the hormones that affect cAMP levels by stimulating AC activity? (7)

Back 30

Epi (beta2)
Glucagon
ACTH
Vasopressin
Follile Stimulating
Thyroid Stimulating
Luteinizing hormone

Front 31

What are the hormones that affect cAMP by inhibiting AC activity? (4)

Back 31

Acetylcholine (muscarinic)
Epi (alpha2)
Angiotensin II
Somatostatin

Front 32

How can cardiac muscle contraction be stimulated by Gs?

Back 32

Alpha subunit of Gs stimulates AC, which increase cAMP level, which stimulates contraction

Front 33

How can cardiac muscle contraction be inhibited by Gi?

Back 33

The Beta/Gamma subunit of Gi inhibits the alpha subunit of Gs. The B/G subunit of Gi also hyperpolarizes the cell using the K+ channels inhibiting contraction force. The Gi alpha subunit inhibits AC.

Front 34

How is the B-adrenergic receptor desensitized by phosphorylation?

Back 34

Gs activates AC and cAMP is produced. This creates PKA, which then acts with BARK to phosphorylate and arrest the receptor (arrestin).

Front 35

What diseases are caused by G protein modifications?

Back 35

cholera, whooping cough, diphtheria

Front 36

How does cholera toxin affect a cell?

Back 36

Cholera gets into the cell at GM1 and A1 is released from the complex. A1 causes the Gs alpha subunit to become ADP-ribosylated and GTP can no longer bind to it. This keeps AC active and there is an increase in cAMP. Loss of salts/water . A1 requires NAD+

Front 37

How does the pertussis toxin affect a cell? (whooping cough)

Back 37

The Gi alpha subunit will become ribosylated and GDP cannot be exchanged for GTP. Gi is locked inactive and AC remains active. cAMP increases and a cough forms. PT requires NAD+