Cell Signaling

Question 1

basic template for cell signaling

Answer 1

primary transduction, relay, amplification, divergence to multiple targets

Question 2

four methods of intercellular communication

Answer 2

endocrine - long distance such as insulin or erythropoeitin

paracrine - signal from one cell to a nehgboring cell

autocrine - when a cell produces a substance that acts on itself

juxtacrine - when a cell sends a signal to a neighbor

Question 3

three mothods of intermolecular communication

Answer 3

2nd messengers

phosphorylation

direct contact

Question 4

switch and timer models

Answer 4

switch - signaling by phosphorylation

timer - signaling by GTP-binding protein

Question 5

two major calsses of receptors

Answer 5

cell surface receptors and intracellular receptors

Question 6

nuclear receptors

Answer 6

ligands pass through membrane and binds to receptor in cytoplasm, which goes to the nucleus and activates transcription

ex. cortisol meade by adrenals during stress

Question 7

membrane receptors

Answer 7

ion channel-linked receptors - facilitate transport of ions in response to ligand binding (ex. acetylcholine receptor)

G-protein-linked receptors - seven transmebrane helicies, associated with a G-protein (ex. adrenergic receptor)

enzyme-linked receptors - receptor itself has eznymatic functions (ex. tyrosine kinases)

other receptors don’t have enzymatic functions or are multimeric

Question 8

cytokine receptors

Answer 8

don’t have enzymatic activity buy but activates other molecules that phosphorylate the receptor and provide adaptor sites for downtream elements

Question 9

notch signaling

Answer 9

juxtacrine receptor where ligand is on once cell and receptor is on another

ligand interacts with receptor and activates a protease, cleaving part of the receptor, taking it to the nucleus wher eit affects transcription

Question 10

second messengers

Answer 10

cAMP, IP3, DG, Ca2+

diffuse throughout the cell for singal amplification

cross-talk and fine tuning

rapidly degraded or consumed

Question 11

receptor binding - saturation, affinity, dose-response

Answer 11

receptors can be saturated depending on ligand concentration

the rate of saturation depends oin on the affinity

there are usually a lot more recepotrs present than necessary for strong signals

can control the response of the cell based on how many receptors are present

Question 12

recycling of receptors

Answer 12

receptors that are used get internalized and sent to endosomes, where they are then degraded in lysosomes or recycled to the cell membrane

Question 13

receptor desnsitization

Answer 13

in the case of G protein receptors, kinases (GRK) phosphorylate the receptor, leading to beta-arresin to bind

this prevents ligand binding and promotes internalization for recycling or degradation

Question 14

types of G proteins

Answer 14

large G proteins - G(s), G(i), Golf, Ggust

small G proteins - Ras, Rho, Cdc42, Rac

other G proteins - dynamin, tubulin

about 1000 types of receptors in the genomes, receptors can be modified to recognize ligands, epending on what parts ar phosphorylated

Question 15

regulators of G proteins

Answer 15

GTP/GDP cycle, inactive state bound to GDP, activated state bound to GTP

GTP exchange factors GEF, GDI)

GTPases (GAP), hydrolysis of the terminal phosphate group

Question 16

heterotrimeric G proteins

Answer 16

composed of alpha, beta, and gamma subunits

alpha subunits bind to guanine nucleotides, and the bta-gamma subunits keep conformations in check

GDP exchange for GTP cause them to dissociate and relay signals

the GTP wills tay active for about fifteen seconds before inactivation occurs

Question 17

Gs

Answer 17

stimulates adenylate cyclase in response to beta-adrenergic, glucagon, PTH

Question 18

Gi

Answer 18

inhibits adenylate cyclases in response to acetylcholine, alpha-adrenergic

Question 19

Gt

Answer 19

activates cGMP phosphodiesterases in response to light

Question 20

Gq

Answer 20

activates phospholipase C in response to chemoattractants and thrombin

Question 21

G13

Answer 21

activates tyrosin kinases in response to thrombin

Question 22

Ggust

Answer 22

activates cNMP phosphodiesterase in response to taste signals

Question 23

Golf

Answer 23

activates adenylate cyclases in response to olfactor signals

Question 24

phosphatidylinositol signaling

Answer 24

G protein activation leads to activated phospholipase C

this cleaves inositol phospholipid to creat inositol-1,4,5-triphosphate and diacylglycerol

IP3 activates calcium channels in the ER which leads to calmodulin and PKC activation

DG leads to activation of PKC

Question 25

cyclic AMP signaling

Answer 25

activation of G protein leads to activation of cyclic AMP, which turns ATP into cAMP

cAMP then activates PKA, which phosphorylates proteins such as CREB in the nucleus and promotes transcription

Question 26

cholera pathway

Answer 26

cholera toxin adds ADP-ribose to Gsalpha, making it slow to hydrolyze the GTP

this increases PKA activation, which leads to a phosphorylated chloride channel that is always open

this leads to profuse, watery, life-threatening diarrhea

Question 27

pertussis pathway

Answer 27

leads to the prolonged activation of Gialpha, locking it in the inactivated state, which prevents it from inhibitiing adenylate cyclase

this leads to the resulting cough

Question 28

Ras and Ras-related GTPases

Answer 28

post-translational modification include farnesylation, geranyl geranylation, which allows it to anchro to the plasma membrane

relay switch that activates pathways, turned on by switching its GDP to a GTP, can then interact with other molecules and stimulate pathways such as the MAPK pathways

Question 29

GTP/GDP recycling of G proteins

Answer 29

GEF/GAP proteins control the activity of many G proteins

GEF - exchanges GDP for GTP

GAP - GTPases that exchange GTP for GDP

Question 30

Rac/Rho/Cdc42 and Rab

Answer 30

Rac/Rho/Cdc42 = cytoskeletal reorganization

Rab = vesicle trafficking

Question 31

receptor and non receptor tyrosine kinases

Answer 31

activation loop phophorylation

dimerization and trans-phosphorylation of tyrosine molecules

responds to many growth factors and comes in a divers range of structures

usually have two subunits split apart

Question 32

regulation of Src kinase

Answer 32

viral kinase, phosphotyrosine residue at the C terminus of tyrosine kinases, recognized by the SH2 domain

An SH3 domain that recognizes a proline rich region, conformational impossibility

As a result of a phosphatase, phosphate group gets cleaved and the kinase becomes active after a conformational change

Question 33

regulation of tyrosine kinases

Answer 33

dissociation of a negative regulatory subunit

displacement of a psudosubstrate motif

displacement of a negative regulatory domain

association with positive regulatory factor

phosphorylation-induced conformational change

activation via proteolytic cleavage

tethering to membrane-associated factors or lipids

translocation to the nucleus

Question 34

insulin receptor

Answer 34

activation by binding to insulin causes phosphorylation of the tail

this attracts docking protein IRS, hwich has domains recognized by other SH2 and PTB domain proteins, leading to downstream activation pathways

Question 35

chronic myeloid leukemia

Answer 35

caused by a 9;22 translocation, which produces Bcr-Abl

this hybrid gene is always on, leading to proliferation of mature and immature white blood cells